QD 

416 

A2 

S3 
1904 


UC-NRLF 


Schreiner,  Oswald 

The  Sesqul terpenes,  a  Monograph 


The  Sesquiterpenes. 


MONOGRAPH 


OSWALD  SCHREINER. 


With  a.  ^Preface  by 


EDWARD  KREMERS. 


MILWAUKEE, 

Pharmaceutical  Review  Publishing  Co. 
1QO4. 


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iber  1882  and 

in  the  German 
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Pharmaceutical  Science  Series* 


EDITED     BY 


EDWARD  KREMERS. 


MONOGRAPHS. 

NO.   9. 


MILWAUKEE. 

Pharmaceutical  Review  Publishing  Co. 

1904. 


The  Sesquiterpenes. 


MONOGRAPH 


OSWALD  SCHREINER. 


With  a  ^Preface  by 


EDWARD  KREMERS. 


MILWAUKEE, 

Pharmaceutical  Review  Publishing  Co. 

1904. 


III 


V  -» 


PREFACE. 


of  the  striking  features  in  the  development  of  organic 
chemistry  hats  been  the  lack  of  attention  given  to  proper 
classification  and  perspective.  Since  the  days  of  Kekule  when  he 
arranged  the  carbon  compounds  into  aliphatic  and  aromatic,  tens 
of  thousands  of  organic  com  pounds  have  been  added  to  our  cata- 
logues, yet  their  proper  classification  has  been  ignored. 

This  is  not  only  true  with  reference  to  organic  chemistry  at  large, 
but  applies  to  a  considerable  extent  to  special  chapters  as  well.  Of 
the  three  larger  works  on  volatile  oils,  which  have  appeared  in 
recent  years,  not  one  classifies  adequately  the  chemical  constituents 
found  in  these  semi-natural  products.  Even  the  chemical  treatise  by 
Heusler,  viz.  "Die  Terpene,"  adopts  an  arrangement  based  upon  un- 
satisfactory traditions  rather  than  in  harmony  with  a  broader 
knowledge  of  organic  chemistry. 

An  attempt  to  catalogue  constituents  of  volatile  oils  according 
to  a  rational  system  of  classification  has  been  made  by  Miss  F.  M. 
Gage,*  the  publication  of  which  has  been  begun  by  the  writer.0  One 
of  the  least  known  groups  of  constituents  ,  of  volatile  oils  are  the 
hydrocarbons  CisH24  commonly  known  as  sesquiterpenes.  Although 
their  practical  importance  now  appears  to  have  been  underestimated. 
their  biological  significance  and  their  chemical  interest  have  never 
been  questioned.  Whereas  much  light  has  been  shed  on  so-called 
terpenes  during  the  last  twenty  years,  the  sesquiterpenes  have  re- 
ceiv^d  much  less  attention.  This  has  been  due  in  no  small  part  to 
the  experimental  difficulties  incident  with  their  investigation. 

*    Thesis  University  of  Wisconsin. 
0   Pharm.   Review,  vols.  11)  and  2O. 


VI 

The  author  of  the  following  monograph  has  not  only  gained 
much  in  overcoming  some  of  the  experimental  difficulties  which  have 
discouraged  other  well  known  investigators  of  the  volatile  oils  and 
their  constituents,  but  he  has  also  done  a  real  service  to  those  in- 
terested in  this  subject  in  compiling  this  monograph.  It  is  true  the 
amount  of  positive  information  is  still  limited.  The  principal  value, 
therefore,  lies  in  the  convenient  form  in  which  this  still  meagre 
positive  information  has  been  brought  together  for  the  future  in- 
vestigator. Not  only  is  the  subject-matter  presented  so  as  to  give 
a  greater  breath  of  view  of  the  entire  field,  but  numerous  suggestions 
as  to  lines  of  investigation  are  indicated.  On  the  one  hand,  this  will 
serve  to  bring  order  into  the  chaotic  condition  of  not  well-character- 
ized sesquiterpenes  which  now  encumber  our  literature  on  the  subject, 
on  the  other  hand,  these  suggestions  indicate  lines  of  synthesis  and 
"Abbau"  which  will  ultimately  enable  the  placing  of  the  better 
characterized  sesquiterpenes  in  a  general  system  of  rational  classifi- 
cation of  the  carbon  compounds  at  large. 

Edward  Kremers. 


TABLE  OF  CONTENTS. 


Page. 
Introduction  ..................................................................................................     1 

GENERAL  PART. 

I.    The  position  of  the  sesquiterpenes  in  the  various  systems  of  classifi- 

cation of  terpenes  at  large  (CsH^x  ..............................................     4 

II.    The  position  of  the  sesquiterpenes  in  the  modern  rational  system 

of  classification  of  hydrocarbons  ..................................................  13 

III.  Classification  and  comparison  of  the  better  known  sesquiterpenes     , 

and  discussion  of  possible  constitution  and  synthesis  .................  17 

IV.  The  occurence  of  sesquiterpenes  in  the  vegetable  kingdom  ................  26 

SPECIAL  PART. 

1.  Araliene  ..................................................................................................  27 

2.  Atractylene  ...........................................................  .................................   32 

3.  Bisabolene  ..............................................................................................  33 

4.  Cadinene  .................................................................................................  34 

5.  Calamene  ...............................................................................................  58 

6.  Caparrapeue  ...........................................................................................  58 

7.  Caryophyllene  .......................................................................................  60 

8.  Cedrenes  .................................................................................................  79 

9.  Clovene  ...................................................................................................  83 

10.  Conimeue  ................................................................................................  83 

11.  Cubebene  ................................................................................................  83 

12.  Galipene  .................................................................................................  84 

1-5.  Gruajene  ......  .  ..................  ........................................................................  85 

14.  Gurjunene  ...............................................................................................  86 

15.  Heveene  ..................................................................................................  87 

16.  Humulene  ...............................................................................................  87 

17.  Ledene  ................................................................  ....................................  95 

18.  Patchoulene  ...........................................................................................  97 

19.  Rhodiene  ............................................................  ...................................  98 

20.  Santalenes  ..............................................................................................  98 

21.  Sesquiterpene  of  Ageratum  Oil  .............................................................  106 

22.  from  Arnyrol  ...................................................................  106 


VIII 

Page. 

23.  Sesquiterpene  of  Angelica  Root  Oil 107 

24.  "  of  Basilicum  Oil 107 

25.  of  Calamus  Oil,  Japanese 107 

26.  "  of  Carline  Thistle  Oil 1.07 

27.  from  Caryophyllene  Dihydrochloride 108 

28.  "  of  Cascarilla  Oil 109 

29.  of  Celery  Seed  Oil 109 

29.  "  of  Citronella  Oil 110 

30.  of  Copaiba  Balsam  Oil,  African Ill 

31.  "  of  Cubeb  Oil 112 

32.  of  Cypress  Oil 112 

33.  of  Erechthites  Oil 112 

34.  "  of  Garlic  Oil 112 

35.  "  of  Hemlock  Needle  Oil 113 

36.  of  Hemp  Oil 113 

37.  "  of  Kampferia  Galanga  Oil 114 

38.  "  of  Kesso  Root  Oil 114 

39.  "  of  Laurel  Berry  Oil 114 

40.  "  of  Lavender  Oil 115 

41.  of  Lemon  Oil 115 

42.  "  of  Linaloe  Oil 115 

43.  "  of  Long  Pepper  Oil 115 

44.  of  Minjak-Lagam  Balsam  Oil.. ....116 

45.  of  Peppermint  Oil,  English 117 

46.  of  Peppermint  Oil,  Japanese 117 

47.  of  Pimenta  Oil 117 

48.  of  Poplar  Bud  Oil -.118 

49.  "  of  Sage  Oil,  English 118 

50.  from  Santonin  and  Santonin  Derivatives 118 

51.  of  Spike  Oil 119 

52.  "  of  Spiraea  Oil 119 

53.  "  of  Valerian  Oil 119 

54.  "  of  Wild  Thyme  Oil 119 

55.  Synthetic  Sesquiterpenes 119 

56.  Trivalerylene 120 

57.  Vetivene 120 

58.  Winterene « 121 

59.  Zingiberene l'2'2 

Index...  ...127 


The  Sesquiterpenes. 

At  monograph*  by  Oswald  Schreiner. 


INTRODUCTION. 

The  volatile  oils  contain  a  large  number  of  hydrocarbons  of  the 
general  formula  (C5H8)x.  This  group  of  hydrocarbons  has  been  de- 
signated by  the  generic  word  terpenes, 1  although  this  term  is 
usually  more  specifically  applied  to  the  subgroup  CioHi6.  According 
to  the  value  of  x  in  the  general  formula,  this  group  of  terpenes  is 
classified  into 

Hemiterpenes,  CsHs, 

Terpenes  proper,  CioHie, 

Sesquiterpenes,  CisH24, 

Diterpenes,  C2oHs2,  and  higher 

Polyterpenes. 

Of  the  hemiterpenes  but  a  single  representative  has  been  found  in 
a  volatile  oil,  namely  isoprene,  in  the  oil  obtained  by  destructive 
distillation  of  caoutchouc  or  gutta  percha.  The  terpenes  proper  and 
sesquiterpenes  are  among  the  principal  constituents  of  the  volatile 
oils.  The  diterpenes  and  higher  polyterpenes  are  more  rarely  found 
and  but  little  studied. 

The  chemical  study  of  the  terpenes  proper  and  of  allied  oxygen 
derivatives  has  opened  up  a  fruitful  field  of  research  and  made  possible 
the  rapid  development  of  the  volatile  oil  industry.  Not  only  has  this 
industry  been  placed  on  a  scientific  and  permanent  basis,  but  pure 
science  as  well  has  profited  greatly,  for  some  of  the  most  important 
theories  in  organic  and  physical  chemistry  have  sprung  out  of,  or 
have  found  a  most  fruitful  field'  in  the  study  of  this  class  of  hydro- 
carbons and  their  derivatives. 

The  first  chemical  derivative  of  a  terpene  was  prepared  by  Kindt 
in  1802  by  the  action  of  hydrochloric  acid  on  turpentine  oil.  The 
preparation  of  hydrochlorides  remained  for  many  years  the  only 

*  Thesis  submitted  for  the  doctor's  degree,  University  of  Wisconsin.  June.  1902. 

i  This  term  appears  to  have  been  introduced  by  Kekul£  in  lHf>6  (from  German 
Terpentin)  and  comprised  all  natural  hydrocarbons*  O]0Hi6.  Later  it  was  made  to 
comprise  all  hydrocarbons,  natural  and  artificial  (C5H8)x.  It  should  not  be  con- 
founded with  the  modern  modified  usage  suggested  by  v.  Baeyer  in  accordance  with 
the  Geneva  Congress  nomenclature.  According  to  his 'suggestion  tetrahydrocymenes, 
CioHi*,  are  ''terpenes."  whereas  dihydrocymenes.  CtoHie  (comprising  but  one  of  the 
numerous  possible  subgroups  of  terpenes.  according  to  the  oldest  conception  of  the 
term),  are  to  be  designated  terpadienes,  because  they  have  two  double  bonds,  hence 
di-enes. 


means  for  the  characterization  of  the  terpenes.  The  results  were, 
however,  so  misleading,  due  to  the  isomerization  which  this  acid  often 
induces,  that  in  1884,  when  Wallach  began  his  researches,  the  liter- 
ature of  the  terpenes  was  in  a  chaotic  condition.  The  pioneer  re- 
searches of  this  investigator,  together  with  the  work  of  his  co- 
laborers  and  followers,  has  brought  order  out  of  chaos. 

The  derivatives  which,  more  than  any  others,  have  made  the 
characterization  and  identification  of  the  terpenes  possible,  have  been 
the  addition  compounds  with  nitrosyl  chloride  and  the  oxides  of 
nitrogen:  the  nitrosochlorides,  nitrosates,  nitrosites  and  nitroso-nitro 
compounds.  With  one  exception,  these  nitroso  compounds  are  very 
reactive,  especially  with  organic  bases,  giving  rise  to  nitrolamines 
which  are  well  crystallized  compounds  of  sharp  melting  points.  By 
the  preparation  of  these  derivatives  most  of  the  terpenes  can  now 
be  readily  identified. 

While  the  terpenes  have  been  so  well  characterized  that  the  de- 
termination of  their  different  modifications  offers  no  particular  diffi- 
culty, and  the  investigation  of  these  hydrocarbons  is  being  continued 
along  sure  and  well  beaten  paths,  the  sesquiterpenes  until  a  very 
recent  date  have  resisted  investigation  along  parallel  lines.  The  con- 
ditions for  the  study  of  the  hydrocarbons  of  the  formula  CisH24  are 
exceedingly  unfavorable.  The  sesquiterpenes  are  thick,  easily  resini- 
fying  liquids  with  a  boiling  point  between  250°  and  280°;  in  short, 
their  properties  are  such  that  they  do  not  invite  investigation. 

In  1887  Wallach-  declared  his  intention  to  study  the  sesquiter- 
penes along  lines  parallel  to  those  which  had  proven  so  successful  in 
the  investigation  of  the  terpenes.  He  reports  at  the  time  on  the  di- 
hydrochloride  of  cadinene  and  on  the  pure  regenerated  cadinene.  In 
1892  he  made  a  second  report,3  in  which  he  characterizes  the  ses- 
quiterpene  of  clove  and  copaiba  balsam  oils,  giving  it  the  name  of 
caryophyllene.  Among  the  characteristic  derivatives  prepared  was  a 
nitrosochloride.  Several  other  sesquiterpenes  are  considered  but  not 
characterized.  Two  years  later  Wallach4  published  some  further  notes 
on  the  sesquiterpen  s,  among  them  a  method  for  the  preparation  of 
caryophyllene  nitrosate.  This  is  his  last  contribution  to  the  subject, 
as  the  methods  which  he  had  used  with  so  much  success  in  the  study 
of  the  terpenes  seemed  to  all  but  fail  in  the  study  of  the  refractory 

a  Ann..  2;{S,  p.  Ml». 
3  Ann.,  271,  p.  L'S,~ 
*  Ann.,  279,  p.  391. 


3 

sesquiterpenes.  At  the  beginning  of  his  last  communication  he  says : 
"Urn  eine  sichere  Unterscheidung  der  Sesquiterpene  zu  ermSglichen, 
die  Isomerie-Verhaltnisse  iunerhalb  der  Korperclasse  klarzustellen  und 
damit  eine  sichere  Grundlage  fur  Arbeiten  iiber  die  Constitutionen 
dieser  Verbindungen  zu  schaffen,  beabsichtigte  ich  in  ahnlicher  Weise 
systematise!!  vorzugehen,  wie  ich  es  bei  der  Gruppe  der  Terpene  get  ban 
babe.  Nachdem  ich  mich  davon  iiberzeugen  musste,  wie  undankbar  eine 
solche  Arbeit  1st,  verzichte  ich  wenigstens  auf  die  systematische  Weiter- 
fiihrung  und  will  vorlaufig  nur  noch  einige  Erfahrungen  mittheilen." 
Chapman's5  experience  with  the  nitroso  derivatives  of  humulene 
seemed  to  indicate  that  the  work  was  not  altogether  hopeless.  Four 
years  after  Wallach  made  his  last  communication  on  the  sesquiter- 
penes, the  study  of  this  group  of  hydrocarbons  was  begun  in  this 
laboratory  and  has  been  continued  steadily  since  1897.  The  results 
bave  been  published  from  time  to  time  in  a  series  of  articles  entitled 
"The  Characterization  and  Classification  of  the  Sesquiterpenes,"  as 
follows : 

1.  True  and  bis-nitroso  addition  products  of  caryophyllene,  by 
Oswald    Schreiner   and    Charlotte  F.  James.     Reported    by  Edward 
Kremers.6 

2.  Nitroso  derivatives  of  caryophyllene  and  cadinene,  by  Oswald 
Schreiner  and  Edward  Kremers.7 

3.  Caryophyllene  and  zingiberene  derivatives,  by  Oswald  Schreiner 
and  Edward  Kremers.8 

4.  Zingiberene   and    its    derivatives,    by    Oswald    Schreiner   and 
Edward  Kremers.9 

The  results  thus  far  obtained  seem  to  show  that  the  field  of  the 
sesquiterpenes  is  not  so  discouraging  as  \Vallach  had  supposed.  By 
the  modification  of  old  methods  or  the  application  of  new  ones, 
gratifying  results  have  been  obtained;  in  fact  the  outlook  has  assumed 
rather  encouraging  aspects.  * 

The  first  points  of  attack  should  naturally  be  the  preparation  of 
characteristic  derivatives,  which  will  allow  us  to  separate,  distinguish 
and  identify  the  individual  sesquiterpenes,  and  then  to  classify  them. 

s  Journ.  Chem.  Soc.,  67,  pp.  54  &  780. 

6  Pharm.  Archives.  1,  p.  209. 

7  Pharm.  Archives    2,  p.  273;  Proc.  Am.  Pharm.  Assoc.,  1899,  p.  158. 

8  Pharm.  Archives,  4,  p.  «1. 

»  Pharm.  Archives,  4,  p.  155;   Proc.   Am.  Pharm.  Assoc.,  49.  p.  329. 

*  The  statement  recently  made  by  Gadamer  (Arch.  d.  Pharm. ,  241,  p  22)  viz. 
that  "little  more  than  the  physical  constants"  of  the  sesquiterpenes  are  known,  is 
not  based  on  facts.  Dr.  Gadamer's  *tudy  of  the  literature  evidently  was  very  super- 
ficial for  he  not  even  copied  the  names  of  the  authors  correctly. 


The  characterization  of  several  of  the  large  number  of  known  ses- 
quiterpenes has  been  accomplished.  Like  investigation  of  those  not 
yet  characterized  will,  no  doubt,  reduce  materially  the  still  consider- 
able number  of  supposedly  different  hydrocarbons.  A  system  for  then- 
classification  is  also  suggested  in  the  body  of  this  report.  This 
system  of  classification  does  not  only  include  the  sesquiterpenes  at 
present  known  and  characterized,  but  being  based  broadly  on  the 
best  principles  of  classification  of  hydrocarbons  in  general,  it  will  in- 
clude all  the  numerous  possible  compounds  of  the  formula  dsH^. 

Only  after  the  characterization  of  the  numerous  isorners  is  ac- 
complished will  it  be  possible  to  study  successfully  the  relation  of 
one  sesquiterpene  to  another,  the  relation  of  these  hydrocarbons  to 
their  oxygenated  derivatives,  and  the  problem  of  their  constitution. 

GENERAL  PART. 

I.    The  Position  of  the  Sesquiterpenes  in  the  Various  Systems  of  Classification 
of  Terpenes  at  large  (C5H8)x. 

Until  quite  recently  the  hydrocarbons  of  the  formula  (C5Hs)x  were 
identified  and  classified  on  the  basis  of  their  physical  characteristics 
alone.  Such  a  system  inevitably  had  to  lead  to  endless  confusion. 
The  hydrocarbon  was  usually  named  according  to  the  plant  from  the 
volatile  oil  of  which  it  had  been  isolated,  or  simply  after  the  volatile 
oil  itself.  Thus,  for  instance,  limonene  was  differently  named,  and 
also  considered  as  a  different  compound,  according  to  the  source 
from  which  it  was  obtained.  The  limonene  in  lemon  oil  was  considered 
as  an  isomer  of  that  in  orange  oil,  that  in  the  oil  of  Citrus  bigaradia 
as  an  isomer  of  that  in  the  oil  of  Citrus  lumia,  and  isomeric  with 
all  these  was  the  limonene  in  caraway  oil,  the  carvene.  Thus  we  find 
in  literature  as  many  as  ten  synonyms  for  limonene,  and  as  many  as 
twenty  synonyms  for  dipentene,  the  optically  inactive  modification 
of  limonene.  Pinene,  as  it  occurs  in  the  various  turpentine  oils; 
camphene;  dipentene,  obtained  from  dipentene  dihydrochloride,  the 
"camphre  de  citron;"  caoutchene,  etc.,  were  also  considered  as  iso- 
merie  with  these.  This  historical  kind  of  quasi-isomerism,  based  on 
the  source  of  the  isolated  hydrocarbons,  might  be  termed  genetic 
isomerism. 

This  large  group  of  supposedly  different  hydrocarbons  was  due 
to  the  fact  that  they  are  very  often  accompanied  in  the  volatile  oils 
by  oxygenated  constituents,  which  are  not  readily  separated  from  the 


hydrocarbons  by  fractional  distillation.  In  other  cases,  two  or  more 
hydrocarbons  are  simultaneously  present  in  the  oil,  and  the  resulting 
hydrocarbon  fraction  was  often  considered  a  distinct  hydrocarbon, 
Thus  it  happened  that  fractions  were  obtained  which  differed  in  odor 
and  physical  characteristics  from  the  hydrocarbons  then  known,  and 
were  at  once  given  specific  names  and  considered  as  isomers  of  the 
others. 

For  a  long  time  no  distinction  was  drawn  between  these  two 
kinds  of  isomerism,  the  genetic,  as  we  have  called  it,  and  the  chemi- 
cal; not  even  when  the  study  of  the  hydrocarbons  revealed  that  the 
turpentine  oils  behaved  quite  differently  from  the  oils  of  the  citrus 
species  toward  hydrochloric  acid  and  other  chemical  agents.  Glad- 
stone (1864)  was  the  first  to  question  this  so-called  genetic  isomerism 
and  to  express  the  idea  that  the  hydrocarbons  of  the  different  citrus 
species  were  not  isomeric  but  identical.  Although  his  conclusions 
were  not  always  correct,  he  nevertheless  produced  some  order  in  this 
chaotic  field  by  his  classification  based  on  physical  properties.  It 
was,  however,  not  until  the  work  of  Tilden  and  especially  that  of 
Wallach  supplied  characteristic  chemical  compounds  that  the  different 
terpene  groups  could  be  identified. 

The  chemical  characterization  and  classification  of  the  terpenes 
proper,  based  on  the  work  of  Wallach  and  others,  has  cleared  up  the 
needless  complexity  of  names  caused  by  a  st3rle  of  nomenclature  based 
largely  on  the  botanical  or  other  source  of  the  hydrocarbon. 

In  the  field  of  the  sesquiterpenes  much  more  remains  to  be  done. 
If  the  names  given  to  hydrocarbons  CisH24  from  different  oils  are 
to  be  regarded  as  standing  for  as  many  sesquiterpenes,  there  are  at 
present  more  than  sixty  of  these  compounds.  The  confusion  accom- 
panying this  genetic  style  of  nomenclature  will,  no  doubt,  be  removed 
with  increasing  knowledge  of  these  substances. 

The  sesquiterpene  of  pepper  oil  has  already  shown  itself  to  be 
identical  with  caryophyllene.  Further  work  will  doubtless  show  many 
of  these  "genetic"  isomers  to  be  identical  with  known  sesquiterpenes, 
and  the  total  number  be  thus  materially  reduced. 

A  classification  of  the  hydrocarbons  of  the  formula,  (C5Hs)x  on 
a  physico-chemical  basis  seems  first  to  have  been  attempted  by 
Schodler.10  According  to  this  rather  popular  writer,  the  "volatile 
oils"  were  divided  into  three  orders  of  cawphenes. 

10  See  Fr.  Gruenling-,  Dissert.,  p.  11,  Strassburg,  1879. 


6 

Camphenes  of  the  I.  order.  These  were  the  natural  hydrocarbons. 
They  differed  from  the  members  of  the  following  orders  in  pos- 
sessing optical  activity. 

Camphenes  of  the  II.  order,  designated  as  campherenes.  These  were 
the  isomeric  modifications  resulting  by  simple  chemical  reactions 
from  the  hydrocarbons  of  the  I.  order.  They  and  their  com- 
pounds were  optically  inactive. 

Camphenes  of  the  III.  order,  designated  as  camphilenes.     These  were 
the   isomeric    compounds  which  resulted  by  more  complex  re- 
actions from  the  foregoing.    They  were  also  inactive. 
Concerning  the  term  camphene  it  may  be  of  interest  to  add  that 
Soubeiran  and  Capitaine11  in  1840  made  the  following  statement  in 
regard  to  the  nomenclature  used  by  them :  "Camphfine  est  pour  nous 
le  nom  generique  qui  reunit  toutes  les  especes  CsHs.    Nous  appliquons 
la  terrninaison  £ne  a  toutes  celles  de  ces  huiles  hydroearbonees  qui 
forment  line  combinaison  solide  avec  1'acide  hydrochlorique.     Nous 
employons  la  terminaison  ifcne  pour  celles  qui  donnent  un  camphre 
liquide." 

Gerhardt12  in  1846,  following  the  system  of  Gmelin,  divided  all 
organic  compounds  into  families  according  to  the  number  of  carbon 
atoms  in  the  compound.  The  hydrocarbons  of  the  general  formula 
(CsH8)x  were  classified  according  to  their  boiling  points  and  vapor 
density  as  follows : 
Camphenes,  belonging  to  the  tenth  family,  CioHio  =  2  volumes  of 

vapor  and  boiling  at  about  160°. 
Paracamphenes,  belonging  to  the  fifteenth  family,  CisEb*  =  2  volumes 

of  vapor  and  boiling  at  about  260°. 
Metacamphenes,  belonging  to  the  twentieth  family,  C2oHa2  — 2  volumes 

of  vapor  and  boiling  at  about  310°. 

Berthelot13  in  1860  showed  these  systems  of  classification  to  be 
entirely  inadequate.     Having  more  particularly  studied  the  optical 
relations  of  the  terpenes,  he  distinguished  between  those  occurring  in 
nature  and  those  obtained  from  the  latter  by  a  number  of  reactions. 
His  classification  was  as  follows : 
I.    Natural  hydrocarbons;  terebenthenes.1* 
II.    Artificial  hydrocarbons  obtained  from  the  natural  hydrocarbons, 


iJ  Journ.  de  Pharm.,  26,  p.  1. 
12  Grundr.  d.  org.  Chem.,  2,  pp.  242,  413,  502. 
is  Chim.  org.  fond.  s.  1.     Synth&se,  2,  p.  731. 
A*  Camphenes  of  the  I.  order  (Schodler). 


1.  By  heat; 

2.  By  the  action  of  acids  or  similar  agents;  terebenes.15 

3.  By  the  formation  of  chemical  derivatives,  such  as  hydrochlor- 
ides  and  hydrates,  and  subsequent  generation  of  the  hydro- 
carbon.    The  members  of  this  group  were  differentiated  into 

a.  Camphenes,16    The  crystallized  monochlorhydrate  gives  by 
careful  decomposition  camphene,  which  crystallizes,  is  opti- 
cally active,  and  yields  with  hydrochloric  acid  the  original 
chlorhydrate. 

b.  Camphilenes.     The   liquid    monochlorhydrate    contains    a 
hydrocarbon  camphilene;   it  is  liquid,  but  is  separated  un- 
changed only  with  difficulty. 

c.  Terpilenes.    These  are  obtained   by  careful  decomposition 
of  the  dichlorhydrates;   they  are,  like  the  dichlorhydrates 
themself,  optically  inactive. 

The  polymers  of  the  terebenthenes  were  designated  as  paratere- 
benthenes,17  polymers  of  the  pyrolenes  as  metapyrolenes. 

Later,  in  1862,  Berthelot18  gave  the  following  classification:  "In 
accordance  with  known  facts,  the  hydrocarbon  CioHie —  e.  g.  tere- 
benthene — may  be  regarded  as  the  starting  point  of  two  series: 

1.  Of  a  monatomic  or  camphol19  series  (monohydrochlorides  or 
chlorine  esters  of  camphol,  CioHiTCl;  camphene,  CioHie;  cara- 
phol  alcohols,  CioHis) ; 

2.  Of  a  diatomic  or   terpil  series  (dihydrochlorides,  CioHisCk; 
terpilene,  CioHie;  hydrate,  .CioH^oOa). 

Each  of  these  two  series  constitutes  a  larger  group,  which  can  be 
divided  into  secondary  series,  the  parallel  and  isomeric  members  of 
whifch  occur  in  twos;  each  has  as  type  an  inactive  hydrocarbon: 
namely  camphene  in  the  first  group;  terpilene  in  the  second." 

The  next  important  classification  is  that  by  Gladstone20  in  1864. 
Although  based  on  physical  properties  alone,  this  system  is  in  its 
main  lines  similar  to  the  later  chemical  system  of  classification.  He 
divided  the  hydrocarbons  (CoHs)x  into  compounds,  I.  CioHie; 
II.  CisH2t;  III.  CaoHaa.  The  hydrocarbons  GioHie  were  subdivided 
into  two  further  groups,  as  is  seen  from  the  following: 

15  Camphenes  of  the  II.  order;  campherenes  (Sehodler). 

J6  Camphenes  of  the  III.  order;  camphilenes  (Schodler). 

'7  Paracamphenes  (Gerhardt). 

is  Compt.  rend.,  r»5,  p.  4'.)(i,  544;   Ann.,  Suppl.  2,  p.  235. 

19  Name  applied  by  Berthelot  to  borneol. 

»o  Journ.  Chem.  Soc.,  17,  p.  1. 


8 

1.  (a)  Sp.  gr.  =  0.846  ;  boiling  point  about  173°;  formula 
(b)  Sp.gr.  =  0.85+;  boiling  point  about  160°;  formula  C 

II.          Sp.  gr.  =  0.90+    to    0.92  +  ;     boiling  point    250—260°; 
formula 


III.          Colophene;  boiling  point  about  315°;  formula  CaoHsa- 
To  group  la  belong  the  hydrocarbons  of  the  citrus  species,  which 

he  considers  identical  rather  than  isomeric.    Group  Ib  consists  of  the 

hydrocarbons  of  the  turpentine  oils,  etc. 

About  this  time  the  word  terpene  was  introduced,  evidently  by 
Kekule.  In  his  Lehrbuch  der  organischen  Chemie  (1866),  II,  p.  437, 
he  says,  "  —  das  Terpentinol  und  die  zahlreichen  mit  ihm  isomeren 
Kohlenwasserstoffe,  welche  im  Allgemeinen  als  Terpene  bezeichnet 
werden  mogen."  The  use  of  the  word  terpene  in  a  larger  sense  is  of 
a  later  date. 

In  a  second  communication  made  by  Gladstone21  in  1871,  he 
makes  a  more  detailed  comparison  of  the  physical  properties  of  the 
respective  groups.  The  table  given  to  show  these  group  differences 
is  of  interest  in  this  connection,  and  is  herewith  reproduced. 


10-Carbon 
Group. 

l.~>-Carl)oii 
Group. 

Colophene. 

Formula 

CaoHaa 

Vapor  density 

4  7 

7  1 

Character  of  liquid  

Limpid 

Viscid 

Very  viscid 

Sp.  gr    at  20°  

0.846—0.880 

0  904—0.927 

0  939 

Refract!  ve  index  for  A  ,  at  20° 

1  Hsj  HTsi<  MI 

1.457—1.407 
-\houti  0  027 

1.488—1.497 
\bout  O  029 

1.5084 
0  08  1 

A  ho  ut  48 

About  4'J 

41 

Boilincr  point 

1(50—170° 

249—200° 

'}  1  5° 

Action  of  sulphuric  acid  
Solubility  in  aqueous  alcohol 

Combination  with  HC1  

Polymerizes 
Freely  soluble 
fCioHie  2I1C1] 
and 
I  CioHie  Hfl  j 

Doubtful 
Sparingly  soluble 

f    Cl5»24   2HCI    | 

v  and  in  smaller  J 
(    proportions   J 

None 
Insoluble 

Very  small 
quantity 

Gladstone  remarks  on  the  table  as  follows:  "It  will  be  evident 
that  the  middle  or  fifteen-carbon  group  is  intermediate  in  all  its  pro- 
perties, and  that  these  groups  do  not  pass  by  insensible  gradations 
into  one  another,  but  are  separated  by  strongly  marked  divisions. 
There  is  no  difference  in  specific  refractive  energy,  and  the  various 


21  .Tourn.  Chem.  Soc.,  25    p.  1;    Pharm.  Journ.,  31,  p.  704. 
*  This  refers  to  expansibility  by  heat. 


9 

members  of  the  ten-  and  fifteen-carbon  groups  at  least  have  powerful 
odors,  and  rotate  the  plane  of  polarization  strongly,  sometimes  in 
one,  sometimes  in  the  other  direction." 

Based  on  the  different  properties  of  the  nitroso  compounds, 
Tilden22  in  1877  divided  the  terpenes,  CioHie,  into  two  groups,  as 
follows : 

1.  Turpentine  group.    Boiling  point  156 — 160°;  melting  point  of 
nitroso  derivatives  124°;  they  form  solid  crystalline  hydrated 
terpin  CioH2o02.H20. 

2.  Orange  group.      Boiling  point   174—176°;    melting  point    of 
nitroso  derivatives  71°;    form  (by  Wigger's  process)  no  solid 
crystalline  terpin  hydrate.23 

Of  the  individual  members  of  the  group  Tilden  says:  "The  liquids 
included  in  each  group  are  allotropic  modifications  of  the  same 
hydrocarbon,  distinguished  one  from  another  by  their  various  rota- 
tory action  on  the  polarized  ray." 

In  1878  Tilden24  set  up  the  following  formula  to  explain  the 
constitution  of  the  terpenes,  which  is  of  interest  as  he  proposes  a 
classification  of  the  terpenes,  CioHiG,  in  connection  with  it: 


C3H7      I 

1 

H      -    -      C      :  :      ( 

i           I 

• 

I        CH3       I 

3  =  i_, 

i     i 

;=  i 

i 

:  -  H 

I.                   a 

«' 

II. 

< 

i 

/ 

III. 


According  to  the  boiling  points,  specific  gravity,  and  the  action 
of  certain  agents,  especially  nitrosyl  chloride,  he  divides  the  terpenes 
into  the  three  classes  indicated  above : 


12  Pharrn.  Journ.,  37,  p.  191. 

2s  This  statement  is  not  correct.  Both  dipentene  and  limonene  produce  terpin 
hydrate.  Comp.  Fluckiger,  Arch.  d.  Pharm.,  222,  p.  362;  also  Kremers,  Am.  Chem. 
Journ.  -- 

24 


.,  '15,  p.  695. 
Ber.,  11,  p.  152. 


10 

I.    Propyl  and  methyl  groups  connected  with  the  carbon  atoms 
a  and  a'. 


•?' 
/3  • 


II.    The  groups  connected  with  /?  and 
III.    The  groups  connected  with  f  and  ?' . 


Armstrong  and  Wright  are,  however,  of  the  opinion  that  this 
explanation  is  insufficient,  and  that  the  camphenes  doubtless  form  a 
fourth  class. 

In  1879  Tilden25  again  distinguished  between  the  low  boiling 
(turpentine  group)  and  the  high  boiling  terpenes  (orange  group). 
The  former  combine  with-  one  molecule,  the  latter  with  two  molecules 
of  hydrochloric  acid. 

In  1886  Gladstone26  reports  on  the  refraction  and  dispersion 
equivalents  of  the  volatile  oils.  Based  on  these  additional  physical 
constants,  he  continues  his  classification  of  these  hydrocarbons.  He 
says:  "It  is  now  generally  accepted  that  the  isomeric  oils  of  the 
formula  CioHi^  fall  into  two  groups— the  terpenes  and  the  citrenes, 
or  isoterpenes.  These  two  groups,  together  with  the  cedrenes, 27 
Ci5H24,  differ  in  boiling  point,  specific  gravity,  and  rotatory  power, 
and  also  in  specific  refractive  and  dispersive  energy."  Based  on  the 
optical  properties,  he  comes  to  the  following  "speculative"  con- 
clusion:28 "That  the  citrenes  differ  from  the  terpenes  by  containing  a 
second  pair  of  doubly-linked  carbon  atoms,  and  that  the  double- 
linking  of  this  second  pair  is  also  analogous  to  that  of  the  defines." 

In  this  statement,  based  on  purely  physical  properties,  we  find 
the  germ  of  the  later  physico-chemical  classification.  Nor  is  the  re- 
cognition of  this  difference  in  the  constitution  of  the  "citrenes"  and 
"terpenes"  entirely  due  to  Gladstone.  Even  the  earliest  investigators 
in  this  field  voiced  this  difference,  not  indeed  in  the  term  of  double 
bonds,  for  the  usage  of  this  term  does  not  date  back  so  far.  Thus 
we  find  distinction  made  between  the  double  saturation  capacity  of 
limonene  and  the  single  saturation  capacity  of  pinene.29  Berthelot30 


25  Ber.,  12,  p.  1131. 

2«  Journ.  Chem.  Soc.,  49,  p.  611. 

27  This  term  appears  to  have  been   introduced   by    Beckett  and    Wright   (Journ. 
Chem.  Soc.,  [3].  1,  p.  6)  in  1876.     They  speak  of  the  hydrocarbons  Ci5H24  as  "ses- 
quipolymerides  of  terpenes,  or  cedrenes,  as  they  may  be  economically  termed.") 

28  Chem.  News,  54,  p.  323. 

29  Soubeiran  and  Capitaine. 

so  Compt.  rend.,  55,  pp.  495  and  544;  Ann.,  Suppl.  2,  p.  236. 


11 

is  perhaps  the  only  one  who,  at  least  for  a  time,  considered  this  dis- 
tinction as  unimportant.  This  same  saturation  idea  is  emphasized 
in  Tilden's31  work  above  cited.  The  modern  classification  based  on 
structural  differences  may,  therefore,  be  said  to  have  had  a  gradual 
development. 

Wallach82  in  1885  proposed  the  following  classification  for  the 
hydrocarbons  of  the  formula  (C5H8)x: 

A.  Hemiterpenes  or  pentenes  of  the  formula  CsHs. 

B.  Terpenes  proper,  CioHie.    This  class  was  subdivided  into  the 
groups:  1)  pinene,  2)  camphene,  3)  limonene,  4)  dipentene,  etc. 

C.  Polyterpenes  (C5H8)x. 

1.  Sesquiterpenes 33  or  tripentenes, 

2.  Diterpenes  or  tetrapentenes, 

3.  Polyterpenes,  (CioHi6)x. 

Briihl34  in  1888  extended  his  researches  on  the  influence  of  the 
single  and  double  linkage  of  carbon  atoms  on  the  refraction  of  light 
to  the  terpenes.  He  found  that  the  terpenes  proper  could  be  classi- 
fied according  to  the  number  of  double  bonds  in  the  compound  as 
follows : 

1     Those  containing  two  double  bonds. 

2.  "  "  one 

3.  "  "  no  "' 

Of  the  sesquiterpenes  Briihl  says:  "Ueber  die  Natur  dieser  Korper 
ist  bisher  nichts  weiter  bekannt,  als  dass  die  Mehrzahl  derselben  nach 
der  Saturationsformel  Cir.Ha*!^  zusammengesetzt  ist.  Moglicher- 
weise  existiren  auch  Sattigungsisomere,  z.  B.  Ci5H24  =  ,  doch  weiss 
man  dariiber  noch  nichts  Bestimmtes.  Eine  durch  Thatsachen  be- 
griindbare  Ansicht  iiber  die  Structurverhaltnisse  der  Sesquiterpene 
lasst  sich  daher  zur  Zeit  nicht  vorbringen." 

The  classification  of  Wallach  and'  of  Briihl  underwent  slight  modi- 
fication with  the  discovery  and  study  of  new  terpenes.  The  insuf- 
ficiency of  this  system  was,  however,  especially  emphasized  by  the 
discovery  by  Semmler  of  a  chain  compound  CioHie,  which  he  called 
an  olefinic  terpene. 

In  the  earlier  classifications  the  sesquiterpenes  were  left  entirely 
out  of  consideration,  and  indeed  beyond  the  classification  into  corn- 


si   Ber.,  12,  p.  1181. 

32  Ann.,  227,  p.  300. 

33  This  appears  to  be  the  earliest  use  of  the  term. 
3*  Ber.,  21,  p.  145. 


12 

pounds,  CioHie,  CisH24  and  C2oHs2,  they  were  scarcely  considered. 
The  terpenes  proper  were  offering  so  much  difficulty  at  the  time  that 
the  study  of  the  higher  boiling  viscous  sesquiterpenes  was  considered 
as  a  hopeless  chemical  problem,  and,  as  is  usually  done  in  such  cases, 
they  were  entirely  omitted  from  any  attempt  at  classification  beyond 
that  necessitated  by  differences  in  molecular  weight, 

In  1892  Wallach35  suggested  a  classification  of  the  sesquiterpenes 
along  lines  similar  to  those  of  the  terpenes.  He  divided  them  into 
two  groups: 

I.    Those  containing  two  double  bonds. 
II.    Those  containing  one  double  bond. 

At  that  time  there  were  only  two  sesquiterpenes  which  were 
characterized,  and  these  only  partially.  Cadinene  belonged  undoubt- 
edly to  the  group  containing  two  double  bonds,  as  its  molecular  re- 
fraction and  dihydrochloride  indicated.  Although  the  molecular  re- 
fraction of  caryophyllene,  the  other  characterized  sesquiterpene, 
showed  two  double  bonds,  Wallach  was  of  the  opinion  that  perhaps 
it  contained  only  one,  because  the  monohydrate  was  a  saturated 
compound.  By  dehydration  this  monohydrate  did  not  yield  caryo- 
phyllene, but  a  sesquiterpene  containing  only  one  double  bond,  and 
called  by  Wallach  clovene. 

As  will  be  pointed  out  in  the  following  chapters,  a  more  extensive 
system  of  classification  will  be  necessary  for  the  sesquiterpenes,  for 
no  system  of  classification  which  is  based  solely  on  the  insufficient 
data  of  imperfectly  known  substances  will  suffice  for  any  length  of 
time.  A  classification  of  the  group  of  hydrocarbons  CioHi6  that  is 
to  prove  more  than  ephemerally  useful  must  be  based  broadly  on  the 
best  classification  of  hydrocarbons  in  general.  This  applies  to  the 
sesquiterpenes  as  well  as  to  the  terpenes  proper.  The  classification 
of  the  terpenes  was  developed  historically  for  a  threefold  purpose. 
First  of  all,  to  show  the  imperfections  of  any  system  that  contents 
itself  with  actual  facts  and  ignores  all  possibilities;  secondly,  because 
the  historical  classification  of  the  sesquiterpenes  naturally  developed 
along  lines  laid  down  for  the  terpenes  proper;  and  thirdly,  because 
the  principles  underlying  a  broadly  rational  classification  of  the  ses- 
quiterpenes are  the  same  as  those  upon  which  the  classification  of 
the  terpenes  proper  is  based,  only  the  conditions  are  more  complex. 

35  Ann.,  271,  p.  296. 


13 

II.    The  Position  of  the  Sesqniterpenes  in  the  Modern  Rational  System  of 
Classification  of  Hydrocarbons. 

If  the  group  of  sesquiterpenes  be  considered  apart  from  any 
connection  with  terpenes  at  large,  but  simply  as  isomeric  hydro- 
carbons of  the  formula  CisH24,  it  will  readily  be  seen  that  in  the 
general  system  of  classification  they  must  come  under  the  formula 
of  saturation  CnH2n — e- 

This  formula  of  saturation  reveals  that,  since  there  are  eight 
unsaturated  carbon  affinities,  there  must  be  four  double  bonds  or 
their  equivalents  in  the  molecule.  If  the  eight  hydrogen  atoms  had 
been  abstracted  from  a  saturated  chain  compound,  CisH32,  in  four 
pairs  from  as  many  pairs  of  neighboring  carbon  atoms,  a  double 
bond  would  be  introduced  between  each  set  of  carbon  atoms  thus 
treated.  In  this  case  the  general  chain-like  character  of  the  hydro- 
carbon would  remain  unaffected.  If,  Jiow^ver,  two  of  the  hydrogen 
atoms  had  been  removed  from  carbon  atoms  not  neighboring,  these 
two  free  affinities  would  unite  and  produce  a  cycle  instead  of  a 
double  bond.  A  cycle,  therefore,  is  the  structural  equivalent  of  a 
double  bond.  Applying  this  principle  to  the  formula  of  saturation 
CnH2n — 6,  it  becomes  evident  that  the  following  groups  of  com- 
pounds must  result: 

I.    Chain  compounds  with  four  double  bonds. 
II.    Monocyclic  compounds  with  three  double  bonds. 

III.  Dicyclic  compounds  with  two  double  bonds. 

IV.  Tricyclic  compounds  with  one  double  bond. 
V.    Tetracyclic  compounds  with  no  double  bond. 

Although  it  will  be  evident  that  in  each  one  of  these  groups  the 
number  of  isomeric  forms  will  be  great,  it  may,  nevertheless,  be  ad- 
visable here  to  point -out  some  of  the  possibilities  of  the  numerous 
isomeric  forms. 

Thus,  for  instance,  in  the  first  group  the  basal  chain,  i.  e.  the 
genus  according  to  the  Geneva  Congress  nomenclature,  first  of  all 
comes  in  for  numerous  isomeric  forms  according  to  the  number  and 
position  of  the  double  bonds.  Numerous  isomeric  forms  of  position 
are  further  indicated  by  the  position  of  the  side  chain  or  side  chains. 
Again  some  of"" the  side  chains,  from  propyl  upward,  may  exist  in 
two  or  more  isomeric  forms.  Finally  one  or  all  of  the  double  bonds 
may  be  in  the  side  chains,  and  their  position  would  again  bring 
about  a  variety  of  isomeric  forms. 


14 


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16 

This  also  applies  in  the  main  to  the  other  groups,  but  here  the 
cyclic  nature  of  the  compound  adds  a  new  factor. 

As  demonstrated  in  Chart  I,  the  monocyclic  group  allows  of  a 
farther  subdivision  into  what  might  be  called  nuclear  types  as 
follows : 

Type  1 :    Three  carbon  atoms  in  the  cycle. 
"     2:    Four        "  "  "  " 

"     3:    Five 

«       4.      gix 

It  is  hardly  necessary  to  go  beyond  the  six-mem bered  cycle,  as 
nearly  all  known  compounds  fall  within  this  limit.  Each  of  these 
nuclear  types  may  be  further  divided  according  to  the  number  of 
double  bonds  in  the  cycle,  as  is  shown  in  the  chart. 

With  the  introduction  of  the  side  chains,  the  position  of  the 
double  bond  or  bonds  with  reference  to  the  chain  or  chains  must  be 
considered  and  the  number  of  possibilities  is  greatly  increased.  If 
the  isomerism  of  the  side  chains  is  also  considered,  the  possibilities 
become  still  greater. 

The  second  chart  shows  the  dicyclic  group,  divided  into  nuclear 
types,  and  the  subdivisions  of  these.  In  this  group  the  isomerism 
becomes  more  complex,  and  for  this  reason  the  types  have  been 
indicated  rather  than  filled  out.  In  this  chart  the  two  cycles  are 
represented  as  being  connected  by  two  carbon  atoms,  thus  forming 
a  compound  nucleus.  It  is  of  course  possible  that  they  be  connected 
by  only  one  carbon  atom,  and  they  may  even  be  connected  by  an 
intervening  chain  of  carbon  atoms. 

With  the  tricyclic  arid  tetracyclic  groups  the  isomerism  in  the 
nuclear  types  becomes  quite  complex,  but  it  must  be  remembered 
that  as  the  isomerism  of  the  nucleus  increases,  the  possible  number 
of  isomers  due  to  the  side  chains  continually  decreases  so  that  the 
total  number  of  isomers  in  a  group  does  not  necessarily  increase 
with  the  number  of  the  cycles. 

The  foregoing  considerations  give  us  a  very  extensive  system  of 
classification  for  the  sesquiter penes.  Based  on  the  formula  of  satura- 
tion, it  includes  every  possible  compound  of  the  formula  CisH24, 
from  a  tetracyclic  to  a  .chain  compound,  and  every  possible  nuclear 
structure.  Although  the  number  of  theoretically  possible  isomers  of 
the  sesquiterpenes  is  exceedingly  large,  amounting  to  many  thous- 
ands, the  number  of  these  compounds  which  will  concern  chemists 


17 


for  a  long  time  to  come  is  far  less.  At  present  we  can  only  hope  to 
classify  the  sesquiterpenes  into  groups  of  chain,  monocyclic,  dicyclic, 
tricyclic  and  tetracyclic  compounds.  In  order  to  accomplish  even 
this  much,  the  sesquiterpenes  must  first  be  well  characterized  and 
identified.  It  is  this  phase  of  the  work  that  is  now  carried  on  in 
this  laboratory.  This  accomplished,  the  compounds  may  be  more 
closely  studied  and  their  structure  determined  if  possible,  thus  assign- 
ing each  member  of  the  group  to  its  proper  nuclear  type. 

III.    Classification  and  Comparison  of  the  Better  Known  Sesquiterpenes  and 
Discussion  of  Possible  Constitution  and  Synthesis. 

The  theoretical  discussion  of  the  possibilities  of  the  formula 
CisHs^  in  the  preceding  chapter  shows  that  the  sesquiterpenes  offer 
a  large  field  for  chemical  research.  Although  the  knowledge  of  this 
class  of  hydrocarbons  is  still  in  its  infancy,  the  experimental  facts 
already  indicate  the  probable  existence  of  representatives  of  four  out 
of  the  five  possible  groups.  The  apparent  existence  of  isomers  in 
this  group  of  compounds,  varying  from  tricyclic  to  chain  compounds, 
offers  a  field  for  investigation  which  for  breadth  is  possibly  not 
duplicated  by  any  other  class  of  isomeric  hydrocarbons. 

In  the  accompanying  table  those  sesquiterpenes  of  which  both 
the  specific  gravity  and  index  of  refraction  have  been  determined,  so 


Group. 

Sesquiterpene. 

Sp.  gr. 

Molecular 
Found 

refraction. 
Calculated 

Tetracyclic. 

62.74 

Tricyclic. 

Cedr(?ti<j 

0.936 
0.930 
0.939 

64.13 
64.77 
64.02 

64.45 

(  J  1  o  VP  1  1  e  
Patchoulene  

Dicyclic. 

Araliene  
Tadinene  
OaparrapfMie 

0.909 
0.918 
0.902 
0.903 
'0.912 
0.910 
0.898 

0.913 
0.914 

65.82 
65.93 
65.85 
66.27 
66.22 
65.92 
66.93 

* 

* 

66.15 

Caryophyllene  
Galipene  

Guajene  
Huimileiie  

Rhodiene  

«-Santalene  

/3-Santaleno  

Monocyclic. 

Bisa.bolene  

0.891 
0.873 

67.35 

67.87 

67.86 

Zingiberene......    . 

Chain. 

fr.  Citroriella  oil  

0.864 

71.43 

69.57 

18 

as  to  make  the  calculation  of  the  molecular  refraction  possible,  are 
given.  The  santalenes  are  also  included  because  their  chemical 
properties  and  specific  gravity  indicate  the  group  to  which  they 
belong.  It  is  to  be  remembered  that  in  only  a  few  cases  has  the 
sesquiterpene  urfder  consideration  been  of  reasonable  purity,  and  the 
physical  constants  are  therefore  not  absolutely  accurate.  Moreover, 
some  of  the  sesquiterpenes  given,  may  in  future  be  found  to  be  iden- 
tical with  one  or  the  other  of  the  better  characterized  sesquiterpenes. 

The  arrangement  of  the  table  shows  at  once  that  the  sesquiter- 
penes fall  into  groups,  both  as  to  their  specific  gravities  and  espe- 
cially their  molecular  refractions.  The  results  are  clearly  in  harmony 
with  the  Landolt-Briihl  theory  of  the  influence  of  double  bonds  on 
the  molecular  refraction,  a  marked  deviation  from  the  exact  quan- 
titative relation  being  found  only  in  the  case  of  the  sesquiterpene 
from  citronella  oil  of  rather  uncertain  purity. 

In  this  classification  the  specific  gravity  is  likewise  of  great  im- 
portance, the  rule  being  that  the  more  unsaturated  'the  sesquiter- 
pene, the  lower  its  specific  gravity.  It  is  thus  seen  that  the  specific 
gravity  alone  will  at  least  indicate  the  probable  class  to  which  the 
sesquiterpene  belongs. 

Another  property  that  seems  to  vary  with  the  constitution  of 
the  sesquiterpenes,  is  the  dispersion,  although  the  data  at  hand  are 
too  meagre  to  more  than  merely  indicate  a  difference  in  dispersive 
power. 

The  position  of  some  of  these  better  known  sesquiterpenes  in  this 
system  of  classification  may  now  be  considered. 

The  tetracycUc  group.  The  members  of  this  group,  containing 
no  double  bonds,  will  be  difficult  to  attack  experimentally  .  at  the 
present  state  of  our  knowledge.  They  cannot  form  halogen  or  hydro- 
halogen  addition  products,  nor  yield  nitroso  addition  products  with- 
out suffering  a  break  in  I  he  cycle.  They  may  yield  substitution 
products  and  thus  be  brought  into  the  realm  of  experimental  chem- 
ical research.  No  members  of  this  group  are  known,  although  it  is 
possible  that  some  of  the  heavy  sesquiterpenes  which  apparently  do 
not  react  with  nitrosyl  chloride,  may  belong  to  this  group. 

The  tricyclic  group.  The  members  of  this  group  have  a  compara- 
tively high  specific  gravity,  ranging  from  0.930  to  0.939.  The 
cedrene  isolated  from  cedarwood  oil  by  Rousset  and  the  clovene  ob- 
tained by  Wallach  from  caryophyllene  hydrate  by  treatment  with 


19 

phosphorus  pentoxide,  in  all  probability  belong  to  this  group. 
Patchoulene,  obtained  by  dehydration  from  patchouly  alcohol,  in 
also  a  member  of  the  tricyclic  group. 

The  dieycUc  group.  This  group  has  a  number  of  representatives 
and  promises  to  be  by  far  the  largest  group.  The  specific  gravities 
of  the  members  of  this  group  fall  between  the  limits  0.898  and 
0.918.  Cadinene  undoubtedly  belongs  to  it,  as  is  shown  by  its  mole- 
cular refraction,  formation  of  a  dihydrochloride  and  general  chemical 
behavior.  Caryophvllene  also  belongs  to  this  group,  as  is  definitely 
shown  by  recent  chemical  and  optical  work.  Kanonnikow,36  however, 
reaches  a  different  conclusion  in  regard  to  both  of  these  hydrocarbons 
which  ought  to  be  briefly  mentioned  here.  Kanonnikow  applies  the 
true  density  of  bodies  to  the  determination  of  constitutional  differ- 
ences. According  to  the  dielectric  theory  of  Clausius-Mosotti,  when 
the  dielectric  constant  (according  to  the  electro-magnetic  theory  of 
light)  is  replaced  by  the  square  of  the  index  of  refraction,  n2,  that 
part  of  the  entire  volume  which  is  occupied  by  the  molecules  only, 
becomes  v  =  ~^^.  From  this  the  true  density  becomes  D  =  ^  = 
•fjiiY  d,  where  d  is  the  usual  density.  Kanonnikow  has  found  by 
calculating  the  product  MD  for  the  hydrocarbons  the  following 
empirical  formula : 

(MD)=39.7n  +  (2n±m)H  — 4H  +  a.  9fl  — b.  6H  —  b1.  26H  — c.  4H, 
in  which  n  is  the  number  of»  carbon  atoms,  Xn  +'  w  the  number  of 
h3rdrogen  atoms,  u  the  number  of  cycles,  b  the  number  of  ethylene 
bonds,  b1  the  number  of  napthalene-ethylene  bonds,  and  c  the  num- 
ber of  acetylene  bonds.  H  is  equal  to  0.967.  By  means  of  this 
empirical  formula,  Kanonnikow  finds  that  cadinene  and  caryo- 
phyllene  have  three  cycles  and  one  ethylene  bond,  in  contradiction 
to  the  optical  and  chemical  results  obtained  with  these  hydrocarbons. 

The  molecular  refraction  of  humulene,  although  slightly  high, 
together  with  the  formation  of  a  liquid  hydrorhloride  which  appears 
to  be  a  di-derivative,  place  it  into  this  group.  The  index  of  refrac- 
tion of  the  santalenes  had  not  been  determined  by  Guerbet,  but  the 
formation  of  liquid  dihydrochlorides  and  general  chemical  behavior, 
as  well  as  the  specific  gravity,  indicate  their  relationship  with  the 
members  of  the  dicyclic  group.  The  specific  gravities  and  molecular 
refraction  of  the  uncharacterizcd  sesquilerpenes,  araliene,  caparra- 
pene,  galipene,  guajene  and  rhodiene,  indicate  two  double  bonds. 

36  Journ.  russ.  phys.-chem    Ges.,  31.  p.  573;   Chem.  Ceotralbl.,  1899,  II,  p.  858. 


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22 

The  monocyclk  group.  The  members  of  this  group  show  a  much 
lower  specific  gravity  than  those  of  the  tricyclic  and  dicyclic  groups. 
Bisabolene  and  zingiberene  probably  belong  to  this  group.  If  bisa- 
bolene  is  a  sesquiterpene  as  its  high  boiling  point  would  seem  to 
indicate,  then  it  must  belong  to  this  group,  for  its  physical  constants 
and  formation  of  a  trihydrochloride  leave  no  doubt  of  the  presence 
of  three  double  bonds.  The  low  specific  gravity  and  molecular 
refraction  of  zingiberene  speak  for  three  double  bonds,  but  its  chem- 
ical derivatives  so  far  prepared  are  not  in  harmony  with  this  con- 
clusion. The  reasons  why  the  optical  method  is, considered  the  more 
trustworthy  in  this  case  is  given  under  zingiberene. 

The  sesquiterpene  found  in  the  oil  of  carline  thistle  by  Sernmler, 
if  not  identical  with  zingiberene,  belongs  at  least  in  the  same  group 
with  it. 

The  synthetic  benzol  derivatives  of  the  formula  Ci5Ho4  belong  in 
this  class.  These  are  the  1  —  methyl  —  4  —  isopropyl  —  2 —  isoamyl 
benzene  prepared  by  Glaus,37  and  the  4 —  octyl  —  1  —  methyl  benzene 
prepared  by  Lipinski.38  The  constitution  of  these  two  compounds 
being  known,  they  can  be  assigned  to  the  proper  nuclear  type. 

The  chain  group.  A  possible  representative  of  this  group  is 
found  in  the  sesquiterpene  isolated  by  jbhe  chemists  of  Schimmel  & 
Co.  from  citronella  oil.  The  sesquiterpene  has  a  specific  gravity 
which  is  even  lower  than  that  of  zingiberene,  and  when  it  is  con- 
sidered that  it  has  been  separated  from  methyl  eugenol,  having  a 
specific  gravity  of  1.047,  this  low  specific  gravity  is  significant.  The 
general  chemical  behavior  is  in  harmony  with  the  view  that  it  is  a 
chain  compound.  Its  molecular  refraction,  as  already  mentioned,  is 
rather  high. 

This  brief  presentation  of  the  possible  members  of  the  various 
groups,  while  still  rather  indefinite,  nevertheless  shows  that  among 
the  sesquiterpenes  there  are  compounds  possessing  widely  different 
properties,  whicli  are  doubtless  due  to  some  such  constitutional 
differences  as  those  suggested  above  for  their  classification. 

A  brief  comparison  of  the  more  important  sesquiterpenes  and 
their  derivatives  may  be  given.  In  the  first  of  the  accompanying 
tables,  a  comparison  of  the  physical  properties  of  the  characterized 
sesquiterpenes  and  the  melting  points  of  their  derivatives  is  presented, 
in  order  to  show  the  analogy  as  well  as  the  differences  between  these 

37  Journ.  f.  prakt.  Chem.,  (2),  46,  p.  489. 

38  Ber.,  81,  p.  940. 


23 

hydrocarbons.  In  the  second  table  a  comparison  of  the  more  im- 
portant uncharacterized  sesquiterpenes,  which  have  received  specific 
names,  and  also  a  few  of  those  which  arc  at  present  only  known  by 
the  name  of  the  oil  from  which  they  are  obtained,  is  likewise  pre- 
sented. These  two  tables  do  not  comprise  nil  of  the  sesquiterpenes, 
but  include  all  those  of  which  anything  definite  is  known.  Of  those 
presented  it  will  be  noticed  that  only  six  are  definitely  characterized 
and  three  others  yield  solid  hydrochlorides  of  definite  melting  points. 
The  second  table  serves  to  show  the  almost  total  absence  of  char- 
acterization by  the  preparation  of  chemical  derivatives.  The  fact 
that  many  of  these  have  received  specific  names  does  not  indicate 
that  their  individuality  is  established ;  some  of  the  unnamed  sesqui- 
terpenes are  in  fact  much  better  known  than  many  of  those-  which 
have  been  named  by  overanxious  investigators. 

Many  of  these  sesquiterpenes  will  doubtless  be  found  to  be  iden- 
tical with  one  or  the  other  of  the  better  characterized  sesquiterpenes, 
or  with  each  other. 

The  comparison  given  in  the  tables  is  also  useful  in  pointing  out 
the  possibility  of  such  identity.  It  was  such  a  comparison  which 
suggested  the  application  of  the  caryophyllene  test  to  the  sesquiter- 
perie  of  pepper  oil,  with  the  result  that  this  hydrocarbon  has  been 
identified.  Such  a  comparison  further  indicates,  for  instance,  that 
araliene  and  the  sesquiterpenes  from  laurel  berry,  hemp  and  valerian 
oils,  may  possibly  be  caryophyllene.  Whether  this  is  true  or  not, 
can  of  course  only  be  decided  by  an  actual  test,  which  can  now  be 
readily  made  by  applying  the  nitrosite  reaction.  The  sesquiterpene 
from  carline  thistle  oil  shows  some  similarity  to  zingiberene,  although 
the  properties  given  are  very  meagre.  Other  comparisons  might  be 
made,  but  these  suffice  to  show  that  much  careful  experimental  work 
remains  to  be  done  before  the  sesquiterpenes  can  be  considered 
sufficiently  characterized  for  their  detection  and  identification. 

In  connection  with  this  classification  based  on  constitutional  dif- 
ferences, it  will  not  be  amiss  to  consider  briefly  the  possibility  of 
ascertaining  the  constitution  of  these  hydrocarbons,  both  by  "Abbau" 
and  by  synthesis.  Several  attempts  have  been  made  to  synthesize 
sesquiterpenes.  In  1867  Reboul39  succeeded  in  polymerizing  valery- 
ene  with  cone,  sulphuric  acid,  obtaining  as  one  of  the  products  a 
hydrocarbon  CisH24,  trivaleriene  (see  this  under  synthetic  sesquiter- 
penes). A  similar  result  was  obtained  by  Bouchardat40  in  1878. 

39  Compt.  rend.,  64,  p.  419;    Ann.,  143,  p.  873. 

*o  Compt.  rend.,  87,  p.  654;   Bull.  Soc.  chim.,  33,  p.  24. 


24 


Wallach41  in  1887  attempted  to  prepare  cadinene  dihydrochloride 
.from  the  polymerization  products  of  pinene,  but  failed.  Thinking 
that  cadinene  might  be  produced  by  polymerizing  a  pentene  rather 
than  a  terpene,  he  tried  various  methods  of  polymerization  on  iso- 
prene,  CsHg.  Although  he  obtained  a  hydrocarbon  boiling  between 
260—  28<)°,  he  was  unable  to  prepare  a  solid  dihydrochloride  from 
the  compound.  In  a  later  article  Wallach42  suggests  several  formulas 
for  terpenes  and  one  for  a  sesquiterpene.  These  formulas  are  based 
on  the  supposition  that  these  hydrocarbons  are,  in  part  atx  least, 
polymerization  products  of  a  pentene.  The  sesquiterpene  he  considers 
as  resulting  from  the  polymerization  of  three  molecules  of  isoprene 
as  shown  by  the  following  formula: 


CH 


H 

TT 

C 

/>* 

c 

HC 

xi-'^ 

1 

HC 

\ 

y< 

Hat/ 

\X     H   \S 

C             C 

H2           H2 

Sesquiterpene. 

CH 


XCH8 


Of  this  formula  Wallach  remarks:  "Bei  einem  derartigen  Aufbau 
wiirden  den  Sesquiterpenen  und  (wie  man  leicht  findet)  auch  den  Poly- 
terpenen  je  zwei  doppelte  Kohlenstoffverbindungen  zukommen,  was 
den  bisher  bekannten  Thatsachen  entspricht."  After  the  exposition 
of  the  possibilities  of  isomeric  hydrocarbons  Ci5H24  in  the  preceding 
chapter  it  is  well-nigh  needless  to  call  attention  to  the  fact  that  the 
above  statement  is  altogether  too  narrow  a  view,  and  is  not  even  sup- 
ported by  the  facts  now  recorded  of  well  characterized  sesquiterpenes. 
The  syntheses  of  the  benzene  derivatives  of  the  formula  CisH24 
by  Glaus43  and  by  Lipinski44  are  of  interest  as  they  furnish  us  with 
sesquiterpenes  of  known  constitution,  but  they  do  not  agree  with 
any  of  the  natural  sesquiterpenes,  which  probably  have  some  cycle 
or  cycles  other  than  that  of  benzene  in  their  nuclear  structure. 

*i  Ann.,  238,  p.  88. 

*2  Ann.,  239,  p.  4U. 

«  Journ.  f.  prakt.  Chem.,  (2),  46,  p.  489. 

4*  Ber.,  31,  p.  940. 


25 


CH3 

C 


CH3 


HC 


HC 


C-CsHn 


'CH 


HC 


CH 


CH 


C3H7  C8Hi7 

Another  line  of  synthesis  for  sesquiterpenes  is  suggested  by  recent 
work  with  cyclo  methyl  hexanone.  Thus  Dorrance45  was  able  to  get 
from  two  molecules  of  cyclo  methyl  hexanone,  CiHi^O,  by  a  series 
of  reactions  the  hydrocarbon  Ci4H22,  to  which  he  assigns  the  formula: 

CH3  CH3 

H2        |  H2 


C 

CH                  C 

CH 

\ 

X)c=c< 

/            \ 

\ 
/ 

C 
H 

C                    C 
H                    H2 

C 
H2 

By  using  one  molecule  of  cyclo  methyl  hexanone  and  one  molecule 
of  a  cyclo  ethyl  hexanone  or  cyclo  dimethyl  hexanone,  it  ought  to 
be  possible  to  obtain  a  hydrocarbon  CisH24,  namely,  a  sesquiterpene. 
While  such  syntheses  would  furnish  us  with  sesquiterpenes  of 
known  constitution  it  is  questionable  whether  they  would  agree  with 
any  of  the  known  natural  sesquiterpenes.  The  problem  of  the  con- 
stitution of  these  compounds  is  a  difficult  one.  It  will  probably  have 
to  be  solved  by  methods  of  oxidation  and  hydrolysis,  that  is.  a 
breaking  down  of  the  complex  structures  into  simpler  compounds, 
the  constitution  of  which  may  be  known  or  more  readily  determined. 
The  oxidation  of  the  sesquiterpenes  has  been  but  little  studied,  and 
that  little  offers  no  clue  as  to  the  nuclear  structure  of  any  of  them. 
If  zingiberene  is  monocyclic,  it  ought  to  be  much  simpler  to  work  on 
it  than  the  members  of  the  dicyclic  group.  Direct  oxidation  with 
permanganate  or  bichromate  yield  very  unsatisfactory  results,  but 
anhydrous  copper  sulphate  seems  to  be  more  favorable  in  its  action. 
Some  preliminary  experiments  show  that  zingiberene  is  very  readily 
oxidized  by  this  oxidizing  agent,  with  the  formation  of  an  oily  body, 
the  nature  of  which  has  not  been  determined. 


Dissert.,  G5ttingen,  1897. 


26 


IV.    The  Occurrence  of  Sesquiterpenes  in  the  Vegetable  Kingdom. 

The  sesquiterpenes  are  usually  found  in  volatile  oils  as  such,  or 
in  the  form  of  sesquiterpene  hydrates,46  alcohols  belonging  to  the  so- 
called  camphor  group.  These  hydrates,  by  dehydration,  give  rise  to 
sesquiterpenes  which  are  rarely  identical  with  a  natural  sesquiterpene, 
being  more  often  distinctive  compounds.  Many  oils,  such  as  cedar- 
wood,  santalwood,  copaiba  balsam,  gurjun  balsam,  ginger,  cubeb, 
etc.,  consist  principally  of  a  sesquiterpene  or  a  sesquiterpene  hydrate. 
The  latter  compound  is  found  more  often  in  oils  distilled  from  old 
drug,  and  thus  appears  to  be  produced  from  the  sesquiterpene  during 
the  ageing  process,  although  the  exact  conditions  for  this  change  are 
not  known.  In  other  oils,  the  sesquiterpene  is  present  in  almost  in- 
significant quantities  only. 

The  occurrence  of  the  sesquiterpenes  in  the  vegetable  kingdom  is 
given  in  a  tabulated  form  in  the  following  pages.  The  arrangement 
is  that  of  Engler's  syllabus  of  plant  classification.  Such  a  tabulation 
shows  that  the  sesquiterpenes  are  very  widely  distributed  as  pro- 
ducts of  plant  life.  The  list  includes  thirty  families,  comprising  fifty- 
six  genera  and  upward  of  sixty-nine  known  species.  The  number  of 
volatile  oils  in  which  sesquiterpenes  have  been  found  is  upward  of 
seventy-four,  some  of  these  being  obtained  from  unknown  botanical 
sources. 

The  lack  of  characterization  of  the  sesquiterpenes  makes  it  im- 
possible to  draw  any  general  conclusions,  but  a  few  interesting  facts 
are  nevertheless  brought  out  by  such  a  tabulation.  In  the  pine  fam- 
ily, for  instance,  it  will  be  seen  that  the  sesquiterpene  cadinene  is  re- 
stricted to  the  needles.  Again,  two  distinct  sesquiterpenes  may  occur 
in  different  parts  of  the  same  plant  as  in  the  case  of  Juniperus  vir- 
giniana,  where  cadinene  occurs  in  the  leaves,  and  cedrene  in  the 
wood.  It  is  also  interesting  to  note  that  closely  allied  species  may 
contain  different  sesquiterpenes,  thus  for  instance,  Piper  nigrum  con- 
tains caryophyllene,  and  Piper  betle  and  Piper  cubeba  contain  cadi- 
nene. 


*6  Under  the  term  sesquiterpene  hydrates  only  alcohols  of  the  formula  CisHgsOH 
are  to  be  understood.  There  seems  to  be  a  tendency  to  designate  all  high  boiling 
alcohols  obtained  from  volatile  oils  as  sesquiterpene  hydrates  This  is  especially 
true  of  the  alcohols  CisHgsOH,  which  are  evidently  not  sesqniterpene  hydrates  at 
all,  but  the  hydrates  of  a  hydrocarbon  Ci5H22  belonging  to  a  series  of  hydrocarbons 
less  saturated  than  the  sesquiterpenes. 


27 

Such  an  arrangement  into  families  may  often  indicate  relation- 
ships between  the  sesquiterpenes  as  well.  Thus,  for  instance,  the  ses- 
quiterpenes  found  in  the  pine  family  are  all,  with  the  exception~of~ 
the  cedrene  from  the  wood  of  Juniperus  virginiana,  cadinene.  The 
close  relationship  between  Acorus  calamus  and  Acorus  spuriosus, 
makes  it  probable  that  the  same  sesquiterpene  is  contained  in  both. 
A  similar  relationship  might  exist  in  the  case  of  the  Copaifera  species, 
Dlpterocarpus  species,  and  others,  although  no  general  conclusion  of 
this  nature  can  be  drawn.  A  botanical  relationship  of  this  kind  can 
merely  indicate  a  possible  chemical  relationship  of  the  sesquiterpenes 
contained  in  the  plant,  but  this  must  in  all  cases  be  substantiated 
by  a  careful  comparison  of  physical  constants,  and  when  possible, 
by  the  preparation  of  characteristic  derivatives. 


SPECIAL  PART. 
1.    Araliene. 

In  1899  Alpers47  reported  on  an  examination  of  the  volatile  oil 
obtained  by  steam  distillation  from  the  rhizome  of  Aralia  nudicaulis 
or  wild  sarsaparilla.  The  greater  portion  of  the  oil  boiled  between 
185  —  195°  (80  mm.)  or  260  —  270°  (at.  p.).  Oxygen  was  present, 
and  the  oil  was,  therefore,  treated  with  metallic  sodium.  About  two 
thirds  of  the  oil  thus  treated  distilled  at  189°  (80  mm.)  or  at  270° 
(at.  p.).  Elementary  analysis  and  vapor  density  determination 
showed  it  to  be  a  sesquiterpene.  From  the  liquid  hydrochloride,  by 
treatment  with  sodium  acetate,  a  sesquiterpene  was  regenerated. 
No  solid  bromide  or  nitrosochloride  was  obtained.  Chloroform  and 
sulphuric  acid  produce  a  purple-red  color,  acetic  acid  and  sulphuric 
acid  a  wine-red  color. 

Alpers  concludes  that  this  is  a  new  sesquiterpene  and  proposes 
the  name  of  araliene,  basing  his  assumption  on  the  physical  proper- 
ties of  a  very  small  and  necessarily  impure  sample,  and  on  his  to- 
tally negative  chemical  results ;  whereas,  a  comparison  of  the  physi- 
cal constants  of  araliene  with  those  of  pure  caryophyllene  renders  it 
not  improbable  that  the  araliene  of  Alpers  is  impure  caryophyllene. 


Ainer.  Journ.  Pharin.,  71,  p.  370. 


28 


I 

3 


Sesquiterpene 
Hydrates. 

I          1 

O                                03 

O 

Cubeb  camphor. 

11 

sS   3 
P  $ 

o> 

P                 § 

II         1    1  1    1  1    - 

,. 

— 

i 

.„„« 

—  « 

•~"«™ 

i 

1  1  1^-  1  1  1  1 

1  1 

i    i    i    i    :    :-g    i    i    :         i    i        i    i 

:    :    :    :    :  O  o      ^^x-v        :    : 

:    :    :  ^   :  J  g       g  ^             : 

j^^l  ill  11    ^ 

F  Ji  i 

Zingiberaceae. 
Kaempferia  galanga. 
Zingiber  officinale  
Piperaceae. 
Piper  nigrum  
"  cubeba  
"  betle  

J-     OJ 

li 

s  * 

o3  '3 

•S  i1 


1    1 


,„„, 

™« 

+" 

•™.H 

i    i 

^^0^0 

1 

I-T 

1 

1            1        - 

:         :    :    :    : 

:         :    : 

j 

•      •  ; 

!        :         i         : 

:         :'::': 

oc     • 

a>    : 

:        &  • 

S       o 

if 

•I    -si 

OQ  cr 

.1  o  1  ^  g 
^PL,  ^oWc. 

"§ 

a  1  .1   | 
•a>^  s.a  .1 

•  C^    ^_i      o            ^    C^ 

§QD   ^S     §O 

Monimiaceae. 
Unknown  species  
Lauraceae. 
Cinnamomum  campho 
Neetandra  caparrapi.. 
Sassafras  officinale  
Lauras  nobilis  (berries 

Rosaceae. 
Spiraea  ulmaria  
Leguminosae. 
Copaifera  officinal  is  an 
"  species  (unk 

Zygophyllaceae. 
Bulnesia  sarmienti  

30 


1       2 


Uncharacterized 
Sesquiterpenes. 

ii 

d 

Bisabolene. 
Conimene. 

& 

c 

0) 

1      II 

f, 

O 

a 

1 

-*• 

—  — 

' 

,„,„„,„„ 

-«^« 

1 

,, 

,UOT,pBO 

1            l 

1 

1 

• 

.    .    . 

.    .    . 

0 

:    :    : 

:    :    : 

1 

m 

L 

S 

00                                     ^3 

Q,                                     ^j 

'3                      o 

!       i 

fl 

:    :    :    : 

:    :    :    : 

5              oi      H 

5,3 

°     i.-s 

eo 

Rutaceae. 
Cusparia  trifoliata.... 
Citrus  limonum  
Citrus  bigaradia  
Amyris  balsamifera.. 

Burseraceae. 
Commiphora  species. 
Boswellia  carterii  
Icica  heptaphylla  
Bursera  aloexylon.... 

=      fsl 

eg               B  »T3 

5   -tfsw 

ccj        *r"    °S  oc  oc  02 

ijlilll  ^ 

a   4)  s   5  S  *•  (g 

.0  §U  ^agg  §« 

^^?S  l^2^  S^ 
^2^2  gp^^-gg 

S'StS  |P«^  « 

riufQ^a" 

||    fl 

•S  o^         2 
e  £        S 
lg       1 

£3*    £c 
psS;  85 

fg*     |g 

>.&.  H       2  ^ 
^             ^ 

31 


Sesquiterpene 
Hydrates. 

Ledum  campho 

Patchouly  alcoh< 

1 

—  "3~ 

^ 

Uncharacterized 
Sfsquiterpenes. 

\    \ 

1 

Rhodiene. 

1    l«r 

P  ,. 

1    1        1 

1 

1 

. 

,„„ 

—  « 

•aua^jtqdo^j  BQ 

'3U9UtpU;J 

1 

1 

1 

i 

1 

1 

i 

cd        :    : 

0        :    : 

OS 

i- 

O! 

"o 

- 

T3 

C3 

iperascen 

OD        :    : 

be        :    : 
B        '    : 
cd      •  :    : 

GO 

T3 

« 

yi          • 

*—  ?*•; 

c  -2 

Um  belli  ferae. 
Apium  graveolens  ... 
Archangelica  offic  na 

03 
03 
3 

Cu 

_O 

i 

53 

^ 
a 

1 

rubricaulis 
Ericaceae. 

Ledum  palustre  

<OJ 

1 

(5 

a 

Convulvulus  scoparii 
Labiatae. 
Lavandula  vera  

spica  
Salvia  officinalis  
Thymus  serphyllum. 
Mentha  piperita.  

arvensis  var 
Pogostemon  patchoi 
Ocimum  basilicum... 

Yalerianaceae. 

Valeriana  officinalis. 

«  «  , 

Compositae. 
Ageratum  conyzoide, 
Solidago  canadensis 

Arternesia  absinthiui 
Erechtllites  hieracifo 

Carlina  acaulis  
Atractylis  ovata  

32 


B.  p. 

Sp.  Rr. 

nD 

[«]D 

Caryophvllene  

136-137° 

0.9030 

1.49976 

—  8.96 

(Schreiner  and  Kremers) 
Aral  ion  6 

(20  mm.) 
270° 

(20°) 
0  9086 

1  49936 

—  7  to  —  8 

Caryophylleiie                                    * 

258-260° 

(20°) 
0  9085 

1  50094 

active. 

(Wallach) 

(15°) 

2.    Atractylene. 

By  dehydrating  atraetylol  with  acid  potassium  sulphate,  Gadamer 
and  Amenomiya,48  obtained  a  sesquiterpene,  to  which  they  applied 
the  name  atractylene.  They  also  obtained  a  second  hydrocarbon 
from  an  oily  chlorhydrate,  prepared  by  acting  on  atraetylol  in  ether 
solution  with  hydrochloric  acid  gas.  This  they  also  designated 
atractylene,  although  the  two  hydrocarbons  had  quite  different  pro- 
perties. Based  on  the  molecular  refractions,  the  authors  conclude 
that  the  two  hydrocarbons  differ  from  one  another  by  a  double 
bond.  However,  as  neither  of  the  sesquiterpenes  was  obtained  in  a 
pure  state,  the  physical  constants  can  hardly  be  relied  upon  to  de- 
cide this  point.  No  chemical  derivatives  were  obtained.  Attempts  to 
prepare  the  hydriodide,  bromide,  and  hydrate  failed.  Although  the 
authors  give  the  misleading  title  of  "atractylene  nitrosochloride"  to 
a  section  of  their  experimental  work,  they  only  obtained  a  greenish 
oil  which  readily  decomposed. 

Physical  properties.  Atractylene  by  dehydration  with  KHSCU: 
B.  p.  260-261°  (760mm.);  d^g  =  0.9154;  df§^  0.9101  nD  =  1.50893. 

Atractylene  from  the  oily  chlorhydrate  prepared  from  atraetylol : 

B.p.  133-141°  (14.5mm.);  d~  =0.9267  nD=1.50565. 
Sesquiterpene  hydrate  yielding  atractylene.    Atraetylol. 

This  sesquiterpene  hydrate  was  obtained  from  the  oil  of  Atracty- 
lis  ovata  Thunb.,  which  becomes  crystalline  shortly  after  being  dis- 
tilled. Neno49  assigned  to  it  the  formula  CioHisO.  but  Gadamer  and 
Amenomiya  give  it  the  formula  Cis^eO.  It  appears  to  react  with 
phenylisocyanate,  hydrochloric  and  hydrobrornic  acids,  iodine,  nitric 
acid,  acetic  acid  and  its  anhydride,  also  with  benzoyl  chloride,  but 
no  characteristic  compounds  could  be  isolated,  nor  are  the  esteriflca- 
tion  results  in  any  case  quantitative.  Atraetylol  readily  splits 

48  Arch.  d.  Pharm.  241,  p.  83. 

*»  Journ.  Pharm.  Soc.  of  Japan,  No.  129,  p.  1074, 


33 

off  water.  On  these  results  the  authors  base  the  opinion  that 
atractylol  is  a  tertiary  alcohol. 

Properties.  Loose,  soft  needles  of  peculiar  odor  and  possessing 
a  bitter,  somewhat  scratching  taste. 

M.  p.  59°;  B.  p.  290—292  (760  mm.);  162°  (15  mm.);  nD  (in 
overcooled  condition)^  1.51029  to  1.51101.  Optically  inactive. 

3.    Bisabolene. 

In  1897  Tucholka50  obtained  from  the  oil  of  bisabol  myrrh  a 
hydrochloride  from  which  he  prepared  a  hydrocarbon,  bisabolene, 
boiling  at  259  —  260.3°.  Analysis  and  molecular  weight  leave  Tucholka 
in  doubt  whether  the  hydrocarbon  is  a  terpene,  CioHie,  or  a  diter- 
pene,  Co0H32.  To  the  hydrochloride,  however,  he  assigns  the  formula 
C2oH32.4HCl.  On  account  of  the  high  boiling  point,  however,  Charabot, 
Dupont  and  Fillet51,  class  bisabolene  with  the  sesquiterpenes,  to  which 
it  doubtless  belongs.  Its  specific  gravity  is  high  for  a  terpene,  but 
rather  low  for  a  sesquiterpene,  and  this,  taken  together  with  the  re- 
fraction, indicates  a  sesquiterpene  with  three  double  bonds.  It  would, 
therefore,  fall  into  the  same  class  with  zingiberene.  The  dispersion 
of  the  two  compounds  is  also  very  close,  being  0.01186  and  0.01278 
respectively,  for  nF  —  nc  .  The  formation  of  a  trihydrochloride, 
Ci5H243HCl  (or  C2oH324HCl,  according  to  Tucholka)  is  in  harmony 
with  this  view.  Whether  the  hydrocarbon  naturally  present  in  the 
oil  is  identical  with  bisabolene  generated  from  the  hydrochloride  is 
not  apparent. 

Preparation.  The  trihydrochloride,  prepared  from  the  oil  as  des- 
cribed below,  is  heated  with  anhydrous  sodium  acetate  and  glacial 
acetic  acid.52  The  hydrocarbon  is  separated  by  steam  distillation, 
washed  with  alkali,  again  distilled  with  steam  and  dried  with  solid 
potassa. 

Physical  properties.  The  colorless  bisabolene  has  the  following 
properties  : 

B.p.259—  260.3°;  di7°  =  0.8914;  nD-  1.4608  ;5»  nF  —  nc  =  0.01186. 

Chemical  properties.  No  chemical  properties  of  the  regenerated 
bisabolene  are  given. 

The  trihydrochloride,  CisHatSHCl,  was  prepared  from  the  crude 


so  Arch.  d.  Pbarm.  235,  p.  292. 
ei  Les  Huiles  Essentielles,  p.  894. 

52  See  Ann.,  239,  p.  24, 

53  Comp.  p.  —  . 


34 

oil.  Hydrogen  chloride  was  passed  into  the  cooled  solution  of  one 
part  of  oil  in  six  volumes  of  anhydrous  ether  until  crystals  separated. 
The  ether  was  then  distilled  off  to  about  %  its  original  volume  and 
the  oily  residue  kept  in  a  freezing  mixture  at— 21°  for  two  days.  At 
the  end  of  this  time  the  reddish  brown  liquid  had  changed  to  a  mass 
of  crystals,  which  were  collected  and  washed  with  cold  alcohol.  The 
crystals  were  purified  by  several  crystallizations,  first  from  alcohol 
and  then  from  ether.  When  slowly  crystallized,  the  trihydrochloride 
separated  in  well  developed,  tabular  crystals  of  hexagonal  habit, 
but  which  belong  to  the  rhombic  system,  as  shown  by  their  optical 
behavior.  M.  p.  79.3°;  [«]D  =  35°  17'  in  chloroform  and  37°  16'  in 
ether  solution. 

4-.    Cadinene. 

Synonyms. 

The  class  names  in  the  older  nomenclatures,  such  as, 

Aetherisches  Cubebenol, 

Paracamphene, 

Cedrene, 

Sesquiterebene, 

Sesquiterebenthene, 

Sesquiterpene, 

and  the  specific  names, 

Cubebene, 
Galipene, 
Amyrene, 
Cadinene. 

Cadinene,  before  it  was  characterized,  is  often  referred  to  in  the 
early  literature  under  the  general  class  name  of  paracamphene,  ses- 
quiterpene,  etc.,  and  also  by  the  name  of  the  oil  in  which  it  occurs, 
for  instance,  "atherisches  Cubebenol."54  The  class  name  of  sesquiter- 
pene  is  still  applied  to  it  even  after  Wallach  had  suggested  the  name 
of  cadinene.  Thus  Wallach  and  Conrady55,  in  giving  the  physical 
constants  of  cadinene  and  its  derivatives,  continually  refer  to  it  as 
"Sesquiterpen"  and  to  .its  derivatives  as  "Sesquiterpen  dihydro- 
chlorid"  etc.  Bornemann  in  "Die  Fliichtigen  Oele,"  published  in  1891  ? 


5*  Schmidt.  Arch.  d.  Pharm.,  191,  p.  22. 
55  Ann.,  252,^).  150. 


35 

does  not  mention  the  word  cadinene,  but  always  calls  it  "Sesquiter- 
pen"  and  thus  fails  to  differentiate  between  different  sesquiterpene^ 
largely,  no  doubt,  because  at  the  time  at  which  he  wrote  exceedingly 
little  was  known  about  the  characteristics  of  any  of  the  other  ses- 
quiterpenes.  This,  no  doubt,  also  explains  why  other  writers  some- 
times use  the  word  cadinene  as  though  it  were  synonymous  with 
sesquiterpene. 

The  word  cubebene  was  formerly  largely  applied  to  this  hydro- 
carbon, because  it  was  first  found  in  oil  of  cubebs.  It  is  now  almost 
universally  replaced  by  the  word  cadinene.  The  designation  cubebene 
is  now  restricted  to  the  sesquiterpene  from  cubeb  camphor. 

Galipene  may  also  be  mentioned  as  a  synonym  for  cadinene. 
This  was  at  first  supposed  to  be  a  distinct  sesquiterpene  by  Beckurts 
and  Troeger50  (1897),  but  its  derivatives  have  been  shown  to  be  true 
cadinene  derivatives.  The  name  is  derived  from  Galipea  cusparia 
St.  Hil.  (Cusparia  trifoliate  Engl.),  the  plant  yielding  angostura 
bark  oil,  in  which  the  sesquiterpene  was  found.  The  designation 
galipene  is  now  apphed  to  another  sesquiterpene  found  in  the  same  oil. 

Amyrene,  as  the  dextrogyrate  sesquiterpene  of  West  Indian 
sandal-wood  oil  from  Amyris  balsamifera  is  called  by  Heine  &  Co.,57 
was  shown  by  Deussen58  to  yield  cadinene  derivatives,  and  may, 
therefore,  be  included  in  the  list  of  synonyms  for  cadinene. 

The  name  cadinene  was  proposed  by  Wallach59  in  1887,  because 
the  dihydrochloride  of  the  sesquiterpene  was  obtained  in  large  quan- 
tities from  oil  of  cade. 

History  and  General  Discussion. 

The  history  of  cadinene  is  closely  connected  with  the  chemical 
study  of  cubeb  oil.  As  early  as  1840,  Soubeiran  and  Capitaine60 
found  this  oil  to  consist  largely  of  a  sesquiterpene  which  yielded  with 
hydrochloric  acid  gas  a  crystalline  hydrochloride  melting  at  131° 
and  being  laevorotatory.  In  1860  Lallemand61  obtained  a  similar 
hydrochloride  melting  at  125°  from  a  sesquiterpene  occurring  in  the 
oil  from  Dvyobalanops  camphora.  Lallemand  regenerated  the  ses- 
quiterpene from  this  hydrochloride  by  treatment  with  lead  oxide  or 


56  Arch.  d.  Pharm.,  235,  pp.  518,  634;   236,  p.  392. 

fi7  List  of  products  exhibited  at  Paris,  1900. 

ss  Arch.  d.  Pharm.,  238,  p.  149. 

59  Ann.,  238    p.  78. 

fil>  .Jonrn.  d.  Pharm.,  2G.  p.  76;    Ann.,  34,  p.  323. 

61   Ann.  d.   Phys.,   (X)  r>7,  p.  401;   Ann.,  114,  p.  193. 


36 

mercuric  oxide  at  100°,  or  saponification  with  alcoholic  potassa- 
This  regenerated  hydrocarbon  boiled  at  260°,  was  strongly  laevo- 
rotatory  and  combined  again  with  hydrochloric  acid  to  yield  the  same 
hydrochloride. 

Schmidt02  in  1870  and  1877  and  Oglialoro83  in  1875,  obtained 
a  hydrochloride  from  cubeb  oil,  melting  at  118°.  Oglialoro  regener- 
ated the  hydrocarbon  by  heating  this  hydrochloride  with  water  to  a 
high  temperature.  The  hydrocarbon  boiled  at  264 — 265°  when  recti- 
fied and  could  be  changed  back  into  the  original  hydrochloride  by 
hydrochloric  acid  gas. 

Wallach64  in  1887  undertook  a  more  detailed  study  of  this  ses- 
quiterpene.  He  found  that  the  corresponding  fractions  of  cubeb, 
patchouly,  galbanum,  savine,  and  cade  oil,  all  yielded  the  same 
dihydrochloride,  melting  at  117—118°.  As  cade  oil  contained  the 
sesquiterpene  in  large  quantities,  Wallach  proposed  for  it  the  name 
of  cadinene.  By  heating  this  dihydrochloride  with  aniline,  or  with 
anhydrous  sodium  acetate  in  glacial  acetic  acid  solution,  the  hydro- 
carbon was  regenerated.  This  regenerated  hydrocarbon  again  yielded 
the  same  dihydrochloride.  He  also  prepared  the  dihydrobromide, 
melting  at  124—125°,  and  the  dihydroiodide,  melting  at  105—106°. 

Since  that  time  the  dihydrochloride  of  cadinene  has  been  obtained 
from  the  high  boiling  fractions  of  many  oils.  These  will  be  considered 
specifically  under  the  heading  of  occurrence.  In  all  these  cases,  how- 
ever, the  formation  and  melting  point,  and  rarely  also  other  pro- 
perties, of  the  dihydrochloride  have  been  the  only  evidence  of  the 
identity  of  the  hydrocarbons  in  these  oils.  In  many  articles,  the 
word  cadinene  is  even  used  as  synonymous  with  any  high  boiling 
fraction,  possessing  the  general  properties  of  a  sesquiterpene,  without 
chemical  identification.  It  is  not  at  all  certain  that  cadinene  really 
exists  in  all  of  these  oils.  Cadinene  is  reported05  to  exist  in  asa- 
foetida  oil,  but  Semmler66  has  shown  in  his  work  that  the  hydrocarbon 
is  not  present  in  the  oil  as  such,  but  is  generated  from  an  oxygenated 
product  by  repeated  treatment  with  sodium.  It  is  likewise  reported67 
to  be  present  in  pepper  oil,  but  the  sesquiterpene  from  this  oil  has 


62  Arch.  d.  Pharm.,  191.  p.  21;    Ber.,  10,  p.  190. 

63  Gazz.  chirn..  5.  p.  567;    Ber.  8,  p.  1357. 
«*  Ann.,  238,  p.  78. 

es  Ann.,   271,   p.  297;   Charabot,   Les   Huiles   Essentielles,   p.   89  t;    Heusler,   Die 
Terpene,  p.  148. 

66  Arch.  d.  Pharm.,  229,  p.  17. 

67  Ber.  v.  8.  &  Co.,  Oct.  1893,  Suppl.  p.  33;   Charabot,    Les   Huiles   Essentielles, 
p.  894;    Heusler,  Die  Terpene,  p.  148. 


37 

be  ui  shown  to  be  caryophyllene  and  not  cadinene  by  Schreiner  and 
Kremers.  68  Several  other  cases  of  this  nature  might  be  mentionedy 
where  the  only  fact  to  warrant  the  assumption  that  cadinene  is  pre- 
sent, is  the  color  reaction  suggested  by  Wallach.  °9  A  color  reaction 
of  this  kind  is  at  best  only  a  mere  indication  of  the  possible  presence 
of  cadinene,  but  is  by  no  means  conclusive. 

Attention  should  here  be  called  to  the  tendency  of  the  terpenes 
proper  to  change  from  one  into  the  other  through  the  action  of 
hydrochloric  acid  and  it  is  not  improbable  that  similar  inversions 
may  take  place  with  the  sesquiterpenes.  As  dipentene  dihydrochloride 
results  under  certain  conditions  not  only  from  pinene  but  also  from 
limonene  and  several  socalled  terpene  hydrates,  so  may  the  sesquiter- 
pene  dihydrochloride  melting  at  118°,  and  called  cadinene  dihydro- 
chloride, result  from  several  distinct  sesquiterpenes  and  their  hydrates. 
Although  cadinene  when  regenerated  from  the  dihydrochloride,  is 
always  strongly  laevogyrate,  the  original  fractions  from  which  the 
hydrochloride  was  obtained  show  a  great  diversity  of  optical  activity, 
many  being  strongly  dextrorotatory. 

Beckurts  and  Troeger70  in  1897  contributed  some  interesting 
observations  which  seem  to  point  unmistakably  toward  inversion  in 
the  group  of  the  sesquiterpenes.  They  succeeded  in  getting  from 
fraction  260—270°  of  angostura  oil  an  oxygenated  product,  CisHaeO. 
This  compound  is  optically  inactive,  readily  splits  off  water  when 
heated  and  is  very  difficult  to  obtain.  For  this  compound  they  pro- 
pose the  name  of  galipol.  From  galipol  and  also  from  fraction 
250—280°,  they  obtained  by  heating  with  acetic  acid  anhydride  in 
a  sealed  tube,  a  sesquiterpene,  which  showed  a  rotation  of  +  18°  in 
a  100  mm.  tube.  From  this  hydrocarbon,  which  they  called  "gali- 
pene,"  they  prepared  a  dihydrochloride  melting  at  114—115°,  and  a 
dihydrobromide  melting  at  123°.  The  original  oil  was  strongly 
laevogyrate,  viz.  —  50° ;  the  alcohol  was  inactive,  and  the  hydro- 
carbon generated  from  the  alcohol,  also  that  obtained  from  fraction 
250—280°  with  acetic  acid  anhydride,  was  dextrogyrate,  viz.  +18°. 
From  this  it  appears  that  an  inversion  of  the  sesquiterpene  in  the 
original  oil  has  taken  place.  In  a  later  article71  they  show  that  by 
the  use  of  different  dehydrating  agents,  entirely  different  results  are 


68  Phann.  Archives,  4,  p.  61;    Proc.  Amer.  Pharm.  Assoc.,  49,  p.  349. 
6»  Ann.,  238,  p.  87. 

70  Arch.  d.  Pharm.,  235,  p.  518. 

71  Arch,  d,  Pharm.,  235,  p.  634. 


38 

obtained  from  the  same  oil.  The  original  oil  was  again  strongly 
laevogyrate;  by  treatment  with  acetic  arid  anhydride  the  optical 
activity  was  changed  to  +20°;  by  treatment  with  phosphorus  pen- 
toxide  it  was  changed  to  — 10°.  Further,  they  were  able  to  isolate 
an  inactive  sesquiterpene  from  the  oil  by  fractional  distillation  and 
treatment  with  phosphorus  pentoxide.  In  a  third  contribution72 
they  report  that  the  dihydrochloride  and  dihydrobrornide  formerly 
reported  as  "galipene"  compounds  are  identical  with  the  correspond- 
ing cadinene  derivatives,  although  they  result  from  a  dextrogyrate 
hydrocarbon,  whereas  the  known  cadinene  is  strongly  laevorotatory. 
This  time  they  suggest  the  name  of  galipene  for  the  inactive  sesqui- 
terpene instead  of  the  dextrogyrate  variety  mentioned  above.  These 
observations  leave  the  identity  of  the  sesquiterpenes  in  angostura 
oil  in  a  very  unsatisfactory  condition. 

Other  cases  of  disagreement  in  physical  properties  similar  to  the 
above  are  on  record.  H.  v.  Soden73  found  a  dextrogyrate  sesquiter- 
pene in  West  Indian  sandal-wood  oil,  which  is  designated  by  Heine 
&  Co.74  as  "amyrene."  Deussen,75  however,  was  able  to  get  deriva- 
tives of  the  laevogyrate  cadinene  from  this  dextrogyrate  hydro- 
carbon. Grimal*  on  the  other  hand,  obtained  dextrogyrate  cadinene 
derivatives,  agreeing  in  properties  with  the  usual  laevogyrate 
forms,  from  a  dextrogyrate  fraction  of  atlas  cedar  oil.  Schimmel 
&  Co.76  found  that  both  the  dextrogyrate  Cuban  cedrela  wood 
oil  and  the  laevogyrate  Costa  Rica  variety,  yielded  large  amounts 
of  cadinene  dihydrochloride.  Reychler77  found  that  the  rotation 
of  the  sesquiterpene  in  ylang  -  ylang  and  cananga  oils  yielding 
cadinene  dihydrochloride  was  greatly  affected  by  the  heat  of 
distillation  under  ordinary  pressure,  the  action  going  so  far  as  to 
produce  an  inversion  in  the  rotation.  This  change  did  not  take 
place  when  the  distillation  was  carried  on  under  diminished  pressure. 
All  these  results  clearly  show  that  inversion  may  take  place  and 
that  at  least  two  different  physical  modifications  of  the  same  ses- 
quiterpene yield  the  same  dihydrochloride.  Identification  based  only 
on  such  a  compound  may,  therefore,  lead  to  wrong  conclusions. 

In  view  of   these  facts  it  appeared  highly  essential   that    other 

72  Arch.  d.    Hharm.,  236,  p.  397. 

73  Pharm.  Ztg.,  45,  pp.  229,  878. 

7*  List  of  products  exhibited  at  Paris  1900. 

75  Arch.  d.    Hharm.,  238.  p.  149. 

*  Comp.  rend.,  135,  pp.  582,  1059. 

76  Ber.  v.  S.  &  Co.,  April  1892,  p.  41. 

77  Bull.  Soc.  chim.,  (3)  11,  pp,  576,  1045. 


89 

derivatives  of  these  sesquiterpenes  be  made  before  considering  thejn 
identical.  The  success  with  the  nitroso  compounds  of  caryophyllene 
led  Schreiner  and  Kremers78  to  attempt  the  preparation  of  similar 
compounds  of  caclinene.  These  attempts  proved  fruitless  at  first, 
but  the  conditions  for  the  formation  and  separation  of  some  nitroso 
derivatives  were  finally  found.  So  far  the  nitrosate  and  nitroso- 
chloride  have  been  prepared;  the  nitrosite  has  not  yet  been  separated 
as  its  solutions  appear  to  decompose  very  readily.  It  is,  however, 
a  noteworthy  fact  that  while  these  two  derivatives  can  now  be  made 
with  comparative  ease  from  the  pure  regenerated  hydrocarbon,  they 
have  so  far  not  been  prepared  from  the  original  fraction,  which 
yielded  the  dihydrochloride  in  large  quantity.  Whether  this  is  due 
to  the  presence  of  impurities  in  the  fraction  or  to  a  difference  in  the 
sesquiterpene  itself,  cannot  be  stated. 

From  the  foregoing  it  will  be  seen  that  while  cadinene  is  reported 
as  widely  distributed,  these  statements  must  be  taken  with  reserve. 
Cadinene  is,  moreover,  reported  in  text  books  and  special  treatises 
on  volatile  oils  and  their  constituents  as  the  only  well  characterized 
and  best  known  of  the  sesquiterpenes.  Such  indeed  was  the  case  at 
the  time  of  publication  of  these  treatises.  The  reverse  is,  nevertheless, 
true  at  present.  Of  the  characterized  sesquiterpenes,  cadinene  really 
comes  last  and  until  further  evidence  is  forth-coming  the  word 
cadinene  ought  to  be  applied  only  to  the  sesquiterpene,  which  has 
been  regenerated  from  the  dihydrochloride  and  not  to  the  fractions 
of  volatile  oils  which  yield  this  dihydrochloride.  The  regenerated 
hydrocarbon  is  well  characterized  and  deserves  a  place  in  chemical 
literature  as  a  chemical  unit,  but  the  compounds  yielding  the  dihydro- 
chloride may  or  may  not  be  cadinene  and  further  study  along  this 
line  is  necessary  before  this  point  can  be  cleared  up. 

Occurrence. 

Under  this  heading  the  oils  in  which  cadinene  has  been  reported 
a,s  a  constituent  will  be  discussed.  The  subject  matter  has  been 
arranged  according  to  the  position  of  the  plants,  from  which  the  oils 
are  obtained,  in  Engler's  Syllabus.  The  list  of  plants  yielding  these 
oils  has  already  been  given  in  the  chapter  on  the  occurrence  of  the 
sesquiterpenes  in  general.  Of  those  yielding  cadinene,  the  list  com- 


78  Pharm.  Archives,  1.  c. 


40 

prises  twelve  families,  including  twenty-one  genera  yielding  twenty- 
seven  distinct  oils. 

The  presence  of  cadinene  in  these  oils  has  in  nearly  all  cases  been 
determined  by  the  formation  of  the  dihydrochloride  melting  at 
117—118°.  The  doubtful  oils,  in  which  cadinene  has  been  erroneously 
stated  to  be  present,  or  where  it  is  at  best  only  indicated  by  means 
of  color  reactions,  have,  for  the  sake  of  completeness,  also  received 
mention  in  this  compilation. 

PINACEAE. 
Pinus  silvestris.    Pine  Needle  Oil. 

According  to  Bertram  and  Walbaum79  the  highest  boiling  frac- 
tions of  the  saponified  oil  of  the  needles  from  Pinus  silvestris,  gave 
with  hydrochloric  acid  gas  a  dihydrochloride  melting  at  118°,  iden- 
tical with  cadinene  dihydrochloride. 

Pinus  montana.    Pine  Needle  Oil. 

Bertram  and  Walbaum80  found  that  the  optically  inactive  frac- 
tions of  pine  needle  oil  from  Pinus  montana  boiling  above  250° 
yielded  cadinene  dihydrochloride  melting  at  118°. 

Picea  excelsa.    Pine  Needle  Oil. 

According  to  Bertram  and  Walbaum  81  the  fraction  of  pine  needle 
oil  from  Picea  excelsa,  boiling  above  260°,  had  a  rotation  of  «D  = 
—  6°  40',  and  yielded  cadinene  dihydrochloride  melting  at  118°. 
Tsuga  canadensis.    Hemlock  Needle  Oil. 

Cadinene  is  mentioned  by  Schimmel  &  Co.,82  and  also  by  Heus- 
ler83  as  a  constituent  of  hemlock  oil,  without,  however,  giving  any 
proof  or  reference.  Bertram  and  Walbaum84  in  1-893  report  the 
presence  of  a  sesquiterpene,  but  did  not  identify  it.  Gildemeister  and 
Hoffmann85  in  1899  still  give  the  sesquiterpene  as  undetermined. 

Abies  alba.    Pine  Needle  Oil. 

According  to  Bertram  and  Walbaum  86  the  saponified  pine  needle 
oil  from  Abies  alba  contains  sesquiterpene  ("Wallach's  Cadinen").87 
No  properties  are  given. 


7s»  Arch.  d.  Pharm.,  231,  p.  300. 
so  Arch.  d.  Pharm.,  231,  p.  297. 
si  Arch.  d.  Pharm.,  231,  p.  296. 

82  Ber.  v.  S.  &  Co .,  Oct.  1893,  Suppl.,  p.   21. 

83  Die  Terpene,  p.  168. 

8*  Arch.  d.  Pharm.,  231,  p.  295. 

85  Die  Aeth.  Oele,  p.  340. 

86  Arch.  d.   Pharm.,  231,  p.  291. 

87  Ber.  v.  S.  &  Co.,  April  1893,  p.  29. 


41 

Cedrus   atlantica,    Algerian  variety  of    Cedrus  libani.    Oil    of  Atlas 

Cedar. 

Grimal*  examined  oil  of  atlas  cedar  and  found  the  light  boiling^ 
fractions  to  contain  cadinene,  which  he  identified  by  preparing  the 
dichlorhydrate,  in.  p.  117—118°,  and  also  the  dibromhydrate,  m.  p. 
124—125°.  Sesquiterpene  alcohols  were  also  present  but  not  identi- 
fied. In  a  second  article  Grimal**  shows  the  sesquiterpene  to  be 
d-cadinene  and  prepares  d-cadinene  derivatives,  from  which  he  again 
regenerates  d-cadinene.  The  sesquiterpene  isolated  by  distillation 
from  the  oil  had  the  following  properties:  dis  =  0.9224;  nD  =  1.5107; 
{a]D  =:  +  48°7';  b.  p.  ==  273-275°. 

Juniperus  communis.    Oil  of  Juniper  Berries. 

According  to  Schimmel  &  Co.88  the  high  boiling  fraction  gives, 
cadinene  dihydrochloride,  melting  at  118°. 

Juniperus  oxycedrus.    Cade  Oil. 

Cade  oil  is  obtained  by  the  destructive  distillation  of  the  wood. 
In  1887  Wallach89  obtained  from  fraction  260—280°  of  cade  oil  the 
same  dihydrochloride  as  from  the  corresponding  fraction  of  cubeb  oil. 
As  the  oil  yielded  large  amounts  of  this  sesquiterpene,  he  proposed 
the  name  of  cadinene  for  the  hydrocarbon.  The  dihydrochloride  ob- 
tained from  this  oil  was  the  starting  point  of  Wallach's  researches 
on  cadinene. 

Troeger  and  Feldmann90  in  1898  attempted  to  prepare  the  di- 
hydrochloride from  cade  oil  in  order  to  compare  the  regenerated 
sesquiterpene  with  the  cadinene  found  in  angostura  oil.  The  fraction 
260—280°  yielded,  however,  only  very  little  of  the  dihydrochloride 
or  dihydrobromide,  showing  that  only  a  small  amount  of  cadinene 
could  be  present.  Repeated  distillation  showed  the  oil  to  consist 
mainly  of  an  inactive  sesquiterpene. 

These  results  agree  with  observations  made  in  this  laboratory. 91 
One  sample  of  oil  gave  excellent  yields  of  dihydrochloride,  another 
only  a  very  small  amount,  and  a  third  gave  none  at  all.  In  all 
these  cases  the  fraction  260—280°  was  used.  These  fractions  were 
slightly  dextrogyrate  in  the  last  two  cases.  The  rotatory  power  of 
the  fraction  from  the  first  oil  had  not  been  determined. 


*  Compt.  rend.,  135,  p.  582. 
**  Compt.  rend.,  135,  p.  1057. 

88  Ber.  v.  S.  &  Co.,  April  1890,  p.  43. 

89  Ann.,  238,  p.  82. 

so  Arch.  d.  Pharin.,  236,  p.  692. 
?i  Not  published. 


42 

Reychler92  noticed  that  the  cadinene  from  ylang-ylang  and 
cananga  oils  suffered  a  great  change  in  rotation  on  being  distilled 
under  ordinary  pressure.  In  one  case  an  inversion  to  a  dextrogyrate 
sesquiterpene  took  place.  Whether  this  dextrogyrate  sesquiterpene 
still  forms  a  hydrochloride,  Reychler  did  not  determine.  It  is  highly 
probable  that  the  results  noticed  by  Troeger  and  Feldmann  and  also 
in  this  laboratory  are  due  to  a  similar  cause.  On  the  other  hand  it 
is"  not  improbable  that  the  sesquiterpene  of  cade  oil  is  not  always 
cadinene,  and  that  another  sesquiterpene  may  often  be  present.  Cade 
oUs  of  greatly  varying  properties  are  to  be  found  in  commerce,  and 
the  oil  is  not  always  distilled  from  the  wood  of  Juniperus  oxycedrus 
only,  but  often  from  mixtures  of  these  with  other  woods. 93 

Cathelineau  and  Hausser04  avoid  the  application  of  direct  heat 
to  the  oil,  but  distill  the  nonphenol  portion  of  the  oil  with  water 
vapor,  and  then  mix  it,  without  further  fraction ation,  with  alcohol  and 
treat  it  with  hydrochloric  acid  gas.95  In  this  way  they  obtained  a 
very  satisfactory  yield  of  dihydrochloride  from  the  oil. 
Jumperus  snbina.  Oil  of  Savin. 

Wallach96  mentions  oil  of  savin  in  the  list  of  oils  from  which  he 
obtained  cadinene  dihydrochloride.  Urnney97  mentions  the  presence 
of  polyterpenes  (?)  boiling  at  226°. 

Jumperus  virgmiana.    Oil  of  Cedar  Leaves. 

According  to  Schimrnel  &  Co.98  the  high  boiling  portions  of  oil 
of  cedar  leaves  contained  cadinene  as  was  shown  by  the  preparation 
of  its  dihydrochloride. 

PIPERACEAE. 
Piper  nigrum.    Black  Pepper  Oil. 

Eberhardt99  in  1887  reported  the  presence  of  a  sesquiterpene  in 
black  pepper  oil.  In  1893  Schimrnel  &  Co.100  mention  cadinene  as  a 
constituent  of  this  oil,  without,  however,  giving  proof  or  reference. 
The  same  is  done  by  Heusler.  *  Schreiner  and  Kremers, 2  however, 
showed  this  sesquiterpene  to  be  caryophyllene  (see  this).  It  is  possible 

9a  Bull.  Soc.  chim.,   (3)   11,  pp.  407,  576,  1045. 
93  Comp.   Pharm.  Rev.,  20,  p.  401. 
9*  Bull.  Soc.  chim.,  (8)  25,  p.  981. 

95  See  under  rlihvdrochloride. 

96  Ann.,  238,  p. '82. 

97  Hharm.  Journ.,  (3)  25,  p.  1045. 

98  Ber.  v.  S.  &  Co.,  April  1898.  p.  13. 
»9  Arch.  d.   Pharm.,  225,  p.  515. 

100   Ber.  v.  S.  &  Co.,  Oct.  1893,  Suppl.  p.  33. 

1  Die  Terpene,  p.  175. 

2  Pharm.  Archives,  4,  p.  61;    Proc.  Amer.  Pharm.  Assoc.,   49,  p.  349. 


43 

that   in  this  case  the  name  cadinene  was  used  as  being  synonymous 
with  sesquiterpene. 

Piper  cubeha.    Oil  of  Cubebs. 

Soubeiran  and  Capitaine3  in  1840  examined  cubeb  oil  and  found 
it  lo  consist  largely  of  a  sesquiterpene.  By  the  action  of  hydro- 
chloric acid  they  obtained  a  hydrochloride  melting  at  131°.  This 
compound  they  called  cubeb  camphor,  after  the  nomenclature  then  in 
use.  This  hydrochloride,  like  the  original  oil,  was  laevorotatory,  but 
to  a  greater  extent.  It  formed  long,  oblique,  rectangular,  tasteless 
and  odorless  prisms. 

Later  observers  found  the  melting  point  of  the  dihydrochloride 
obtained  from  oil  of  cubebs  at  118°  and  not  131°  as  reported  by 
Soubeiran  and  Capitaine.  The  latter  also  state  that  it  was  readily 
soluble  in  cold  alcohol,  whereas  all  other  observers  especially  mention 
its  slight  solubility  in  cold  alcohol.  Nevertheless,  these  authors  in 
all  probability  had  impure  cadinene  dihydrochloride  under  con- 
sideration. 

In  1870  Schmidt4  obtained  from  the  laevogyrate  fraction  of 
cubeb  oil  boiling  about  250°,  a  dihydrochloride,  CisEbj^HCl,  melting 
at  120 — 125°.  In  1877  he  states  that  the  dihydrochloride  melts  at 
118°.  5 

Oglialoro6  in  1875  found  in  cubeb  oil  a  laevogyrate  "sesquiter- 
eben,"  CisEbi,  boiling  at  264 — 265°,  which  yielded  a,  hydrochloride 
melting  at  118°.  By  heating  with  water  to  a  high  temperature,  the 
hydrochloride  was  decomposed  and  yielded  the  original  hydrocarbon. 
He  also  obtained  a  second  hydrocarbon,  boiling  at  a  somewhat  lower 
temperature,  viz.  262—263°;  it  was  less  active  optically  and  gave 
no  hydrochloride.  This  latter  hydrocarbon  was  probably  an  impure 
fraction  of  the  same  "sesquitereben"  as  even  this  distilled  over  at  a 
temperature  nearly  ten  degrees  below  the  boiling  point  of  pure 
cadinene.  This  is,  however,  by  no  means  certain,  as  it  may  very 
easily  happen  that  two  sesquiterpenes  occur  in  the  oil,  analogous  to 
the  occurrence  of  several  terpenes  in  one  oil.  Later  researches,  how- 
ever, do  not  mention  this  second  sesquiterpene,  although  Schmidt7 
in  1870  also  mentioned  "eine  Modification  des  atherischen  Cubeben- 


s  .Tourn.  d.  Pharm  ,  26,  p.  76;    Ann.,  34,  p.  323. 

*  Arch.  d.  Pharm.,  191,  p.  21. 

s  Ber.,  10,  p.  190. 

«  Ber.,  8.  p.  1357. 

7  Arch.  d.  Pharm.,  191,  p.  22. 


44 

61s"   (sesquiterpene)  which  absorbs  hydrochloric  acid  but  does  not 
combine  with  it. 

Piper  betle.    Oil  of  Betel  Leaves. 

Eykman8  in  1889  isolated  from  Java  betel  oil  a  hydrocarbon 
boiling  about  260°.  Analysis  and  molecular  weight  determination 
indicated  the  formula  CisH24.  It  had  a  specific  gravity  of  0.917  at 
13°;  nD  —  1.50400.  The  indices  of  refraction  for  the  three  hydrogen 
lines  are  also  given.  The  molecular  refraction  indicates  two  double 
bonds.  Bromine  and  hydrochloric  acid  in  acetic  acid  produce  a  deep 
indigo-blue  color.  No  chemical  work  is  reported. 

The  chemists  of  Schimmel  &  Co.9  isolated  a  fraction  from  Siam 
betel  oil  boiling  between  250—275°.  It  is  described  as  having  a. 
pleasant  tea-like  odor  and  consists  principally  of  cadinene  ("cubebene") 
as  was  shown  by  the  preparation  of  its  dihydrochloride  melting  at 
117-118°. 

The  betel  oil  investigated  by  Eykman  differed  somewhat  in  general 
composition  from  that  of  Schimmel  &  Co.,10  but  the  sesquiterpene 
found  by  Eykman  is  probably  also  identical  with  cadinene.  The 
properties  of  cadinene  and  Eykman's  sesquiterpene  are  given : 

B.  p.  Sp.  gr.  nD 

Sesquiterpene about  260°       0.917  (13°)        1.50400 

(Eykman) 
Cadinene 274—275°       0.918(20°)        1.50647 

(Wallach) 

Although  cadinene  has  been  identified  with  certainty  only  in  Siam 
oil,  it  is  no  doubt  also  present  in  the  other  commercial  varieties. 

ANONACEAE. 
Cananga  odorata.    Ylang-Ylang  and  Cananga  Oil. 

Reychler11  isolated  from  ylang-ylang  oil  a  fraction  boiling  at 
138—143°  (20  mm.)  which  had  the  specific  gravity  0.910  at  15°  and 
index  of  refraction  1.50001  at  20°.  The  rotatory  power  was  observed 
as  -|-46.40  in  a  two  decimeter  tube,  but  the  author  is  inclined  to 
think  that  the  rotation  was  —133.6°,  as  the  original  oil  was  strongly 
laevogyrate.  This  would  make  [a]D  —  —73.4°  for  the  hydrocarbon. 


s  Ber.  22,  p.  2736. 

»  Ber.  v.  S.  &  Co.    April  1889,  p.  6;   Journ.  f.  prakt.  Chem.,  89,  p.  349. 
10  See  Ber.  v.  S.  &  Co.,  April  1890.  p.  6. 
"   Bull.  Soc.  chim.,  (3)  11,  pp.  407,  576. 


45 

This  sesquiterpene  yielded  with  hydrochloric  acid  a  dihydrochloride 
melting  at  117°. 

In  a  second  distillation12  of  the  same  oil  the  author  obtained  a 
corresponding  fraction  of  decidedly  different  rotatory  power.  This 
fraction  was  obtained  by  distilling'  several  times  under  atmospheric 
pressure.  The  boiling  point  was  250 — 255°,  specific  gravity  0.9125 
at  18°;  n  =  1.50380;  [«]D  =  +6.8°  in  a  9.1  p.  c.  alcoholic  solution. 
Keychler  thinks  this  dextro-rotation  to  be  due  to  an  inversion  during 
the  process  of  distillation  under  atmospheric  pressure.  Whether  or 
not  this  dextrogyrate  fraction  gave  a  dihydrochloride  like  the  laevo- 
gyrate  fraction  of  the  first  distillation  is  not  stated. 

In  a  third  communication  Reychler13  reports  on  cananga  oil. 
He  isolated  from  it  a  fraction  boiling  at  139.5— 145°  (20  mm.).  It 
had  a  specific  gravity  of  0.9024;  n  =  1.50187;  [a]D  =  —32.2°. 
This  same  substance  when  distilled  under  atmospheric  pressure 
shows  the  following  properties  :  specific  gravity  0.9057  ;  n  =  1.50103; 
[«]D  =  —1.25°.  This  shows  that  the  rotatory  power  of  the  sesqui- 
terpene suffers  greatly  by  heat  as  already  observed  under  ylang-ylang 
oil.  No  hydrochloride  was  prepared  from  this  sesquiterpene,  although 
it  is  probably  identical  with  that  found  in  ylang-ylang  oil,  namely, 

cadiriene. 

MONTMLACEAE. 

Unknown  Moniwiaceae.    Paracoto  Bark  Oil. 

Wallach  and  Rheindorff14  showed  the  presence  of  cadinene  in 
paracoto  bark  oil  by  the  preparation  of  the  dihydrobromide  melting 
at  121°.  From  this  they  regenerated  the  sesquiterpene  and  prepared 
the  dihydrochloride  melting  at  118°  and  having  a  rotation  of  — 33.5°. 

LAURACEAE. 

Cinnamomum  camphora.    Oil  of  Camphor. 

Schimmel  &  Co.15  isolated  from  the  high  boiling  fractions  of 
camphor  oil,  a  sesquiterpene  boiling  at  260—270°,  which  yielded  a 
hydrochloride  melting  at  117°,  the  same  as  that  of  the  dihydro- 
chloride of  cadinene,  "cubebene." 

Sassafras  officinalis.    Sassafras  Oil.    Sassafras  Leaf  Oil. 

Power  and  Kleber16  made  a  very  thorough  examination   of  an 

12  1.  c.,  p.  582. 

is  Bull.  Soc.  chim.,  (3)  11,  p.  1045. 

i*  Ann.,  271,  p.  800. 

is  Her.  v.  S.  &  Co.,  April  1889,  p.  i). 

is  Pharm.  Review,  14,  p.    102 


46 

authentic  oil  of  both  the  bark  and  leaves.  From  each  of  these  oils 
they  obtained  a  small  fraction  (about  3  p.  c.  in  the  case  of  the  oil 
from  the  bark)  distilling  between  260—270°.  "In  this  the  presence 
of  cadinene  was  presumed,  as  it  gave  in  glacial  acetic  acid  solution 
with  a  trace  of  sulphuric  acid  the  violet  coloration  which  is  charac- 
teristic for  this  sesquiterpene."  No  solid  hydrochloride  could,  how- 
ever,- be  obtained,  so  that  the  presence  of  this  sesquiterpene  must  be 
left  in  doubt. 

RUTACEAE. 

Cusparia  trifoliata.    Angostura  Bark  Oil. 

Beckurts  and  Troeger17  obtained  from  angostura  bark  oil  a 
laevogyrate  sesquiterpene,  the  hydrohalogen  addition  products  of 
which  agreed  in  melting  point  and  rotation  with  the  corresponding 
cadinene  compounds.  A  sesquiterpene  showing  all  the  properties  of 
cadinene  could  be  generated  from  them. 

Beckurts  and  Troeger  also  isolated  a  liquid  sesquiterpene  hydrate, 
CisHanO,  which  they  called  galipol  (see  this).  This  alcohol  is  inactive 
optically  and  has  not  been  definitely  characterized.  The  authors 
produced  by  heating  it  with  acetic  acid  anhydride  in  a  sealed  tube 
to  170°,  a  dextrogyrate  sesquiterpene,  to  which  they  gave  the  name 
of  "galipene."  The  impure  fractions  of  the  oil,  consisting  of  galipol 
and  sesquiterpenes,  gave  the  same  hydrocarbon  when  subjected  to 
this  treatment.  This  socalled  "galipene"  gave  a  hydrochloride  melt- 
ing at  114—115°  and  a  hydrobromide  melting  at  123°.  These  com- 
pounds were  shown  to  be  identical  with  the  corresponding  cadinene 
derivatives  in  a  later  report.18  The  authors,  therefore,  discard  the 
name  of  "galipene"  for  this  dextrogyrate  sesquiterpene  and  apply  it 
to  a  third  sesquiterpene  found  by  them  in  the  oil.  This  is  inactive, 
optically,  and  not  sufficiently  well  characterized  to  warrant  the 
authors  to  apply  a  specific  name  to  it. 

That  this  socalled  "galipene''  is  an  inversion  product  is  shown 
by  the  fact  that  the  original  oil  is  strongly  laevogyrate  ( — 50°)  but 
when  heated  with  acetic  acid  anhydride  it  becomes  dextrogyrate 
(18—20°).  With  phosphoric  acid  anhydride  it  is  reduced  to  —10°. 
Distillation  under  atmospheric  pressure  alone  will  change  the  rotation 
from  strongly  laevogyrate  to  dextrogyrate.19  Reychler20  observed 


IT  Arch.  d.  Pharm.,  235,  pp.  518,  634;    236,  p.  392. 

is  Arch.  d.  Pharm.,  236,  p.  397. 

is  Ar.-h.  d.   Pharm.,  236,  pp.  404,  407. 

20  Bull.  Soc.  chim.,  (3)  11,  pp.  582,  1045. 


47 

a  similar  inversion  in  the  distillation  of  the  sesquiterpene  from  ylang- 
ylang  and  cananga  oils  (see  these)  and  found  it  to  be  due  to  the 
heat  of  distillation  under  atmospheric  pressure.  When  distilled  in  a 
vacuum  this  inversion  did  not  take  place.  Inasmuch  as  Beckurts 
and  Troeger  distilled  almost  entirely  under  atmospheric  pressure, 
these  different  optical  results  can  by  no  means  be  taken  as  evidence 
that  chemical  individuals  were  under  consideration. 

Citrus  bigaradia.    Oil  of  Petitgrain. 

According  to  Semmler  and  Tiemann31  petitgrain  oil  contains  a 
high  boiling  sesquiterpene.  Charabot  and  Fillet22  state  that  the 
residue  above  232°  deposited  a  crystalline  substance,  the  quantity  of 
which  was  too  sm  ill  to  analyse.  The  liquid  portion  of  this  residue 
gave  the  color  reaction  for  cadinene  with  glacial  acetic  acid  and 
sulphuric  acid,  thus  indicating  the  possible  presence  of  this  sesqui- 
terpene. 

Amyris  balsamifera.    West  Indian  Sandalwood  Oil. 

H.  v.  Soden23  reports  the  presence  of  sesquiterpenes  in  West 
Indian  sandalwood  oil.  This  sesquiterpene  fraction  Heine  &  Co.24 
call  "amyrene"  after  the  name  of  the  genus  yielding  the  oil.  In  view 
of  Deussen's  work,  however,  they  suggest  that  amyrene  is  d-cadinene, 
although  Deussen25  obtained  all  three  hydrohalogen  derivatives  of 
1-cadinene  from  the  oil.  The  dihydrochloride,  dihydriodide  and 
dihydrobromide,  agreed  in  melting  point,  composition  and  optical 
rotatory  power  with  the  corresponding  derivatives  of  cadinene  deter- 
mined by  Wallach.  A  peculiarity  is  that  the  oil,  and  also  the  ses- 
quiterpene according  to  Heine  &  Co.,  is  dextrogyrate,  whereas  laevo- 
gyrate  cadinene  derivatives  are  obtained  from  it.  This  is  similar  to 
the  results  obtained  by  Beckurts  and  Troeger20  with  angostura  oil. 

BURSERACEAE. 

Boswellia  carterii  and  other  species.    Oil  of  Olibanum  (Frankincense). 
Wallach  and  Walker27  mention  cadinene  as  occurring  in  oil  of 
olibanum. 


21  Ber.,  25,  p.  1186. 

22  Bull.  Soc.  Chim.,  21,  p.  74. 

23  Pharm.  Ztg.,  45,  pp    229.  878. 

2*  List  of  products  exhibited  at  Paris,  1900. 

25  Arch.  d.   Pharm.,  238,  p.  149. 

26  Arch.  d.  Pharm.,  235.  pp.  518,  634;    236,  p.  392. 

27  Ann,,  271,  p.  297, 


48 
MELIACEAE. 

Cedrela  species.    Oil  of  Cedrela  Wood. 

According  to  Schimmel  &  Co.28  Cuban  cedrela  wood  oil  contains 
large  amounts  of  cadinene,  as  was  shown  by  the  preparation  of  the 
dihydrochloride  melting  at  118°.  The  rotation  of  the  original  oil 
was,  however,  dextrogyrate,  «D  =  + 18°  6'. 

Punta  Arenas  (Costa  Rica)  cedrela  wood  oil  likewise  consists 
principally  of  a  sesquiterpene  yielding  cadinene  dihydrochloride  melt- 
ing at  118°. 29  The  rotation  of  this  oil  was  to  the  left,  «D  =  —  5°  53'. 

The  other  commercial  varieties  of  cedrela  wood  oils,  Corinto, 
La  Plata,  and  Porto  Alegre  are,  like  the  foregoing  oils,  light  blue  or 
yellowish  in  color  and  probably  also  consist  largely  of  sesquiterpenes. 

D1PTEROCAEPACEA  E. 
Dryobalanops  c amphora. 

Lallemand30  in  1860  found  in  the  oil  of  Dryobalanops  camphora 
a  sesquiterpene  which  boiled  between  255  and  270°,  the  larger  amount 
distilling  at  260°.  The  specific  gravity  changed  in  this  interval  of 
temperature  from  0.90  to  0.921  at  20°,  and  the  rotation  changed 
from  slightly  laevo-  to  dextrogyrate  and  increased  up  to  the  fraction 
going  over  at  265°,  when  it  again  decreased,  the  portion  distilling 
at  270°  being  inactive.  With  hydrochloric  acid  it  yields  a  crystalline 
compound,  CioH24.2HCl,  melting  at  125°.  This  compound  rotated 
the  ray  of  polarized  light  always  to  the  left,  no  matter  whether  it 
was  obtained  from  a  dextro  or  a  laevorotatory  portion  of  the  oil. 

Lallemand  regenerated  the  sesquiterpene  from  this  dihydro- 
chloride by  treatment  with  lead  oxide  or  mercuric  oxide  at  100°,  or 
saponification  with  alcoholic  potassa.  This  regenerated  hydrocarbon 
boiled  at  260°,  was  strongly  laevogyrate  and  combined  again  with 
hydrochloric  acid  to  yield  the  same  dihydrochloride.  Although  the 
melting  point  of  this  dihydrochloride  as  reported  is  rather  high  for 
cadinene  dihydrochloride,  it  is  nevertheless  very  probable  that  Lalle- 
mand had  this  compound  under  consideration. 

UMBELLIFERAE. 

Ferula  asa,  foetida  and  other  species  of 
Ferula  and  Peucedanum.    Oil  of  Asafetida. 

Cadinene  does  not  occur  as  such  in  asafetida  oil,  but  is  obtained 
from  an  oxygenated  constituent  by  repeated  treatment  with  sodium. 

28  Ber.  v.  S.  &  Co.,  April  1892,  p.  41. 

29  1.    C. 

so  Ann.  chim.  phys.,  (3)  57,  p.  401;   Ann.  114,  p.  193. 


49 

This  oxygenated  constituent  was  isolated  from  the  oil  bySemmler31 
and  had  a  boiling  point  of  113—145°  (9  mm.);  d22°  =  0.9639-; 
«D  =  —16°.  Analyses  corresponded  to  the  formula  _  (CioHieO)n. 
This  oxygenated  constituent  gave  by  repeated  distillation  with  me- 
tallic sodium  an  oil  which  corresponded  in  composition  and  vapor 
density  to  a  sesquiterpene.  It  had  the  following  properties :  an  odor 
resembling  lavender;  b.  p.  123°  (9  mm.);  di5°  =  0.9241.  With 
hydrochloric  acid  gas  it  yielded  a  dihydrochloride  having  the  melting 
point  116°,  nearly  identical  with  that  found  for  cadinene  dihydro- 
chloride. 
Ferula  rubricaulis  and  other  species.  Oil  of  Galbanum.  f 

Oil  of  galbanum  is  mentioned  by  Wallaeh32  as  yielding  large 
amounts  of  cadinene  dihydrochloride. 

LABI  ATA  E. 

Men  t  ha  piperita.    American  Oil  of  Peppermint. 

From  the  high  boiling  fractions  of  American  peppermint  oil, 
Schimmel  &  Co.33  obtained  a  fraction  boiling  about  260°,  which 
yielded,  when  treated  with  hydrochloric  acid  gas,  a  solid,  crystalline 
dihydrochloride,  melting  at  118°,  identical  with  cadinene  dihydro- 
chloride. 

English  oil  of  peppermint  also  contains  a  sesquiterpene,  but  no 
hydrochloride  was  prepared.34 

Pogostemon  patchouli.    Oil  of  Patchouly. 

Oil  of  patch ouly  is  mentioned  by  Wallach35  as  containing  large 
quantities  of  cadinene.  The  fraction  -  270—280°  yielded  a  large 
amount  of  the  dihydrochloride. 

COMPOSTTAE. 

SoMago  canadensis.    Oil  of  Golden  Rod. 

According  to  Schimmel  &  Co.36  cadinene  is  found  in  the  oil 
distilled  from  SoMago  canadensis.  They  do  not  state  on  what 
evidence  the  conclusion  is  based. 

Artemisia  absinthium.    Oil  of  Wormwood. 

The   presence   of   cadinene  in  fraction  260—280°  was  shown  by 

31  Arch.  d.   Pharm.,  229,  p.  15;    Ber.,  23,  p.   3532;    24,  p.  80. 

32  Ann.,  238,  p.  81. 

33  Bericht  S.  &  Co..  April  1894.  p.  42. 

3*  Pharm.  Journ..  (8)  11,  p.  220;   Arch.  d.  Pharm.,  218, 'p.  222. 

35  Ann.,  238,  p.  81. 

36  Bericht  S.  &  Co.,  April  1897,  p.  53. 


50 

Schimmel  &  Co.37  by  the  formation  of  its  dihydrochloride  melting  at 

117—118°. 

Preparation. 

Cadinene  has  not  been  isolated  in  a  pure  state  from  any  of  the 
oils,  the  socalled  cadinene  fractions  of  these  oils  in  fact,  showing 
widely  different  properties.  These  fractions  serve  for  the  preparation 
of  the  dihydrochloride  of  cadinene  as  will  be  described  below.  From 
the  purified  dihydrochloride,  the  hydrochloric  acid  is  again  split  off 
and  pure  cadinene  regenerated. 

As  early  as  1860  Lallemand38  regenerated  the  hydrocarbon  from 
the  dihydrochloride  by  treatment  with  lead  oxide  or  mercuric  oxide 
at  100°,  or  saponification  with  alcoholic  potash.  Lallemand  deter- 
mined the  boiling  point  of  the  regenerated  hydrocarbon  at  260° 
found  it  to  be  strongly  laevogyrate  and  to  yield  the  same  hydro- 
chloride  when  treated  with  hydrochloric  acid  gas.  Oglialoro39  in  1875 
attempted  to  prepare  the  pure  hydrocarbon  by  heating  the  hydro- 
chloride  with  water  to  170—180°  for  some  time.  He  obtained  a 
hydrocarbon  boiling,  when  rectified,  between  264—265°  and  again 
yielded  the  same  dihydrochloride  melting  at  118°. 

In  1887  Wallach40  subjected  the  dihydrochloride  to  a  more  de- 
tailed study.  The  dihydrochloride  had  been  obtained  from  fraction 
260 — 280°  as  described  under  cadinene  dihydrochloride,  and  from  this 
the  hydrocarbon  was  regenerated.  According  to  this  investigator  the 
hydrochloric  acid  can  be  split  off  by  two  methods41,  either  of  which 
is  more  satisfactory  than  the  methods  employed  by  Lallemand  or 
Oglialoro. 

1.  With  aniline.    20  g.  of  the  pure  hydrochloride  are  warmed 
with  twice  this  weight  of  aniline  for  a  few  minutes,  until  the  forma- 
tion of  aniline  hydrochloride  takes  place.    When  the  reaction  is  com- 
plete the  excess  of  aniline  is  removed  by  shaking  with  hydrochloric 
acid.    The  hydrocarbon  is  then  distilled  with  steam  and  after  drying 
with  solid  potassium  hydrate,  it  is  rectified  by  distillation.    Almost 
the  entire  amount  passes  over  from  274—275°. 

2.  With  anhydrous  sodium  acetate.    A  mixture  of  20  g. 
of  the  pure  dihydrochloride  with  20  g.  of  anhydrous  sodium  acetate, 
are  treated  with  80  cc.  of  glacial  acetic  acid,  and  heated  in  a  flask 

37  Bericht  S.  &  Co.,  April  1897,  p.  51. 

38  Ann.  chim.  phys.,   (3)   57.  p.  401;    Ann..  114,  p.  193. 

39  Gazz.  chim.,  5,"  p.  567;    Ber.,  8.  p.  1357. 

40  Ann.,  1238,  p.  78. 

*i  Ann.,  238,  pp.  80,  84. 


51 

provided  with  a  reflux  condenser.  At  first  a  clear  solution  results, 
but  after  a  few  minutes  the  separation  of  sodium  chloride  begins 
and  in  less  than  half  an  hour  the  reaction  is  complete.  On  cooling 
a  part  of  the  hydrocarbon  separates  out  at  the  surface  and  by  the 
addition  of  water,  the  entire  amount  of  the  sesquiterpene  separates. 
By  washing  with  water,  or  better  by  shaking  with  some  solution  of 
sodium  hydrate  and  subsequent  distillation  with  steam,  the  cadinene 
is  obtained  in  a  pure  state.  After  drying,  the  cadinene  distills  con- 
stant at  274—275°  as  with  the  first  method. 

Physical  Properties. 

The  physical  constants  given  under  this  heading  apply  only  to 
the  regenerated  cadinene  and  not  to  any  so-called  cadinene  fractions 
obtained  from  volatile  oils.  For  the  properties  of  these  fractions  the 
respective  oils  must  be  consulted  under  the  heading  of  occurrence. 

As  already  mentioned  both  Lallemand  and  Oglialoro  had  the 
regenerated  sesquiterpene  in  hand.  The  boiling  points  given  by  both 
these  investigators  is  low,  Lallemand's  being  260°  and  Oglialoro's 
264—265°,  whereas  Wallach  found  it  to  be  274—275°.  Wallach  42 
explains  this  difference  of  ten  degrees  in  the  boiling  point  by  the  fact 
that  the  method  used  by  Oglialoro  could  hardly  have  separated  all 
of  the  hydrochloric  acid  and  that  the  hydrocarbon  under  considera- 
tion was  not  pure.  Moreover,  Wallach 's  results  are  all  stated  for  a 
corrected  boiling  point  and  for  this  reason  would  be  somewhat 
higher.  The  same  argument  will  doubtless  apply  to  Lallemand's 
results,  whose  hydrochloride  could  not  have  been  pure  to  start  with, 
as  it  melted  at  125°  instead  of  118°. 

The  physical  constants  as  found  by  Wallach  and  Conrady43  are 
as  follows:  B.  p.  274—275°;  di6°  ==  0.921,  d20  ==  0.918;  u^  = 
1.50647;  [«]„  —  —98.56°  in  a  13.05  p.  c.  chloroformic  solution. 

Beckurts  and  Troeger44  regenerated  from  the  hydrobromide  ob- 
tained from  angostura  bark  oil  a  sample  of  cadinene  which  was 
evidently  less  pure  than  that  obtained  by  Wallach.  Its  physical 
constants  were:  B.  p.  264—269°  (uncorr.);  di9°  =  0.9240;  nDi9° 
--  1.5079Q;  [«]»  ==  -88°  37'. 

Grimal*  obtained  from  the  oil  of  Cedrus  atlantica  a  hydrochloride 
from  which  he  regenerated  the  dextro  variety  of  cadinene.  This  re- 

*2  Ann.,  238.  p    80,  tootnote. 

43  Ann.,  238,  p.  85;    252,  p.  150:    271,  p.  297. 
**  Arch.  d.  Pharm.,  236,  p.  396. 
*Compt.  rend.  185,  pp.  582,  1057. 


52 

generated  d-cadinene  had  the  following  properties:  b.  p.  274 — 275°; 
di5°=0.9212;  nD  =  1.5094;  [o]D  =  +  47°  55'. 

The  molecular  refraction  of  cadinene  calculated  from  the  index  of 
refraction  indicates  two  double  bonds. 

Pure  cadinene  is  a  colorless,  rather  limpid  liquid,  having  an  odor 
that  is  not  unpleasant.  It  shows  a  great  tendency  to  resinify  when 
exposed  to  the  air,  the  liquid  becoming  very  viscous  in  a  few  days. 
Schreiner  and  Kremers45  found  that  if  cadinene  is  kept  in  contact 
with  solid  caustic  potash,  it  will  retain  its  original  characteristics 
for  several  months. 

Cadinene  is  soluble  with  difficulty  in  alcohol  and  glacial  acetic 
acid,  but  dissolves  readily  in  ether. 

Chemical  Properties  and  Derivatives. 

Cadinene  yields  with  the  hydrohalogens  well  characterized  addi- 
tion products  which  retain  the  laevo-rotation  of  the  pure  cadinene, 
but  are  less  active.  The  dihydrohalogen  addition  products  are  quite 
stable  and  are  readily  crystallizable,  except  the  dihydriodide  which 
is  decomposed  by  alcohol  and  can  only  be  obtained  in  a  pure  form 
by  crystallizing  from  anhydrous  solvents.  According  to  Deussen46 
the.  stability  decreases  from  the  hydrochloride  to  the  hydriodide  when 
heat  is  applied. 

Cadinene  also  yields  a  nitrosate  and  a  nitrosochloride.  On  oxi- 
dation .  with  chromic  acid  it  yields  man}^  of  the  lower  fatty  acids, 
which  are  volatile  with  water  vapor.  When  allowed  to  drop  slowly 
into  cold  fuming  nitric  acid,  a  lively  reaction  takes  place  and  each 
drop  is  dissolved.  By  pouring  into  water  and  washing,  a  yellow, 
solid  compound,  which  is  soluble  in  caustic  alkali  and  cannot  be 
crystallized,  is  obtained. 

Cadinene  gives  a  very  fine  color  reaction  when  it  is  dissolved  in 
much  chloroform  and  drops  of  sulphuric  acid  are  added.  The  chloro- 
form becomes  green,  then  blue,  and  on  heating  changes  to  red.  The 
reaction  is  still  more  striking  when  the  cadinene  is  dissolved  in  much 
acetic  acid  and  cone,  sulphuric  acid  is  added  drop  by  drop.  This 
color  reaction  is  only  very  faintly  shown  by  the  pure,  recently 
distilled  hydrocarbon,  while  resinification  is  very  favorable  to  it.  It 
may  be  of  interest  to  add  that  the  radinene  preserved  for  several 


Pharm.  Archives,  2.  p.  299;    Proc.  Ainer.  Pharm.  Assoc.,  47,  p.  180. 
Arch.  d.  Pharm.,  238,  p.  155. 


53 

years  with  solid  causfcic  potash  as  above  stated,  gave  this  reaction 
so  faintly  that  it  could  scarcely  be  recognized,  whereas  another 
sample,  not  so  treated  .  and  completely  resinified,  gave  an  intense" 
reaction.  This  color  reaction  is  therefore  not  characteristic  of  the 
pure  sesquiterpene,  but  depends  on  the  products  of  oxidation,  accom- 
panying it  as  an  impurity.  The  reaction  is  very  useful,  however,  as 
an  indication  of  the  presence  of  this  sesquiterpene,  but  can  hardly  be 
accepted  as  a  proof. 

According  to  Wallach47  cadinene  appears  to  be  changed  by  con- 
tinued heating  with  dilute  sulphuric  acid. 

Cadinene  dihydrochloride,  CisH^SHCl.  The  dihydro- 
chloride  was  first  obtained  by  Soubeiran  and  Capitaine48  from  cubeb 
oil  in  1840  and  was  called  by  them,  cubeb  camphor,  melting  at  131°. 
In  1860  Lallemand49  obtained  a  dihydrochloride  melting  at  125° 
from  the  oil  of  Drynbalanops  camphora.  Schmidt50  in  1870  and 
1877  and  Oglialoro51  in  1875  again  obtained  this  compound  from 
cubeb  oil.  Both  report  the  melting  point  of  118°. 

Wallach52  in  1887  obtained  this  dihydrochloride  from  the  high 
boiling  fractions  of  cubeb,  patchouly,  galbanum,  savin  and  cade  oils. 
According  to  Wallach  the  dihydrochloride  is  best  prepared  from  oil 
of  cade  as  follows : 

Crude  oil  of  cade  is  distilled  with  steam  under  pressure  and  the 
distillate  freed  from  phenols  by  shaking  with  alkali.  'The  nonphenols 
are  then  dried  over  solid  caustic  potash  and  rectified.  Fraction 
260 — 280°  is  diluted  with  twice  its  volume  of  ether,  saturated  with 
dry  hydrochloric  acid  gas  and  allowed  to  stand  for  several  days. 
At  the  end  of  this  time,  the  ether  is  distilled  off  on  a  water  bath  or 
allowed  to  evaporate  spontaneously.  From  the  residue  la.rge  amounts 
of  the  dihydrochloride  crystallize  out.  The  crystals  are  collected  on 
a  force  filter  and  washed  with  cold  alcohol.  By  recrystallization 
from  hot  ethyl  acetate  and  washing  with  alcohol,  the  substance  is 
obtained  in  small  but  pure  crystals.  By  allowing  it  to  crystallize 
slowly  from  a  solution  in  ordinary  ether,  the  dihydrochloride  can  be 
obtained  in  well  developed  rhombic  hemihedral  prisms. 53 

Another    method,   which    is    especially   well  suited    for   preparing 

*7  Ann.,  271,  p.  297. 

48  Journ.  d.   Pharm.,  26,  p.  7(5:   Ann.,  34,  p.  823. 

49  Ann.  chiin.  phys.  (3)  57,  p.  401  :    Ann..  114,  p.  193. 
so  Arch.  d.    Pharm.,   191,  p.  21;    Ber.,  10,  p.   190. 

si  Gnzz.  rhim.,  5,  p.  467;    Ber.,  8,  p.   1357. 

52  Ann.,  238,    p.  78. 

53  For  crystallographic  measurements  by  Hintze  nee  Ann.,  238,  p.  83. 


54 

small  quantities  is  to  add  to  a  solution  of  the  hydrocarbon  in  acetic 
acid,  some  fuming  hydrochloric  acid,  or  better  a  solution  of  the  gas 
in  acetic  acid.  After  shaking  for  a  short  time  the  dihydrochloride 
crystallizes  out. 

Troeger  and  Feldrnann54  have  met  with  difficulty  in  preparing 
the  dihydrochloride  from  oil  of  cade.  This  same  difficulty  was  ex- 
perienced in  this  laboratory  and  has  already  been  discussed  under 
oil  of  cade  in  the  section  on  occurrence.  The  difficulty  is  due  either 
to  the  fact  that  the  sesquiterpene  yielding  the  dihydrochloride  is  not 
always  present  in  the  oil,  or  else  it  has  undergone  changes  during 
distillation  as  Reychler55  has  shown  in  the  case  of  ylang-ylang  and 
cananga  oils. 

In  order  to  avoid  the  application  of  direct  heat  to  the  oil,  Cathe- 
lineau  and  Hausser 56  .proceed  as  follows: 

Oil  of  cade  is  freed  from  phenols  with  caustic  soda  solution  and 
the  nonphenols  distilled  with  steam.  This  distillate,  without  previous 
fractionation,  is  then  mixed  with  three  times  its  volume  of  90  p.  c. 
alcohol.  The  oil  is  only  slightly  soluble  and  settles  to  the  bottom. 
A  very  rapid  current  of  dry  hydrochloric  acid  gas  is  then  passed 
into  the  cooled  mixture  until  saturated,  when  it  is  allowed  to  stand 
for  twenty-four  hours  in  a  cool  place.  At  the  end  of  this  time  the 
oil  at  the  bottom  will  be  found  to  have  formed  a  magma  of  crystals. 
These  are  collected  and  washed  with  a  little  alcoholic  hydrochloric 
acid  and  finally  with  absolute  alcohol.  They  may  be  purified  by 
recrystallization  from  a  little  hot  absolute  alcohol. 

The  pure  dihydrochloride  is  obtained  in  white  crystals  which  are 
sparingly  soluble  in  cold  alcohol,  more  so  in  ether  and  in  hot  alcohol. 
It  is  readily  soluble  in  hot  ethyl  acetate  from  which  it  crystallizes 
on  cooling. 

Cadinene  dihydrochloride  melts  at  117—118°  and  according  to 
Wallach  and  Conrady,57  [«],>  = —36.82°  in  a  7.212   p.    c.    chloro- 
formic  solution.    Beckurts  and  Troeger58  found  [a],,  =  —37.3°  in  a 
7.91    p.    c.    chloroformic   solution,  and    Deussen59    reports    [«]„  = 
— 36.65°  in  a  3.358  p.  c.  chloroformic  solution.    These  three  samples 


5*  Arch.  d.  Pharm.,  236,  p.  692. 

55  Bull.  Soc.  chim.,  f3)  11,  pp.  407,  576,  1045. 

56  Bull.  Soc.  chim.,  (3)  25,  p.  931. 

57  Ann.,  252,  p.  150. 

58  Arch.  d.  Pharm.,  236,  p.  398. 

59  Arch.  d.  Pharm..  238,  p.  153. 


55 

of  dihydrochloride  had  been  obtained  from  cade,  angostura  bark  and 
West  Indian  sandalwood  oils  respectively. 

By  treating*  with  aniline  or  anhydrous  sodium  acetate  in  glacial 
acetic  acid  solution,  the  cadinene  'can  be  regenerated  as  was  men- 
tioned above.  This  regenerated  cadinene  again  yields  the  same 
dihydrochloride  when  treated  as  above,  or  with  a  solution  of  hydro- 
chloric acid  gas  in  glacial  acetic  acid. 

The  d-cadinene  dihydrochloride  obtained  by  Grimal*  from  the 
oil  of  Cedrus  atlantica  had  the  following  properties:  in.  p.  117—118°; 
[a]D  =1  +  8°  55'  in  chloroform  solution  and  +  25°  40'  in  acetic 
ether  solution. 

According  to  Wallach  and  Walker60  cadinene  dihydrochloride, 
when  heated  with  hydriodic  acid  (sp.  gr.  1.96)  for  15  hours  to 
180 — 200°,  yields  a  saturated  hydrocarbon,  CisH^s,  having  the  fol- 
lowing properties:  b.  p.  257—260°;  dis  =  0.872;  nD  =:  1.47439. 

Cadinene  dihyd'robromide,  Ci5H242HBr.  This  compound 
can  be  prepared  in  a  manner  analogous  to  that  used  in  the  prepara- 
tion of  the  dihydrochloride.  According  to  Wallach61  it  forms  very 
readily  when  a  solution  of  cadinene  in  glacial  acetic  acid  is  treated 
with  fuming  hydrobromic  acid.  Deussen62  prepared  it  by  shaking 
the  hydrocarbon  with  twice  its  volume  of  ether  saturated  with  hydro- 
bromic acid,  and  Beckurts  and  Troeger63  by  shaking  with  ten  times 
its  volume  of  a  saturated  solution  of  hydrobromic  acid  in  glacial 
acetic  acid.  The  dihydrobromide  can  be  recrystallized  from  ethyl 
acetate.  It  forms  white  crystals  melting  at  124 — 125°.  According 
to  Wallach  and  Conrady,6*  [«]D  =  —36.13°  in  a  7.227  p.  c.  chloro- 
formic  solution.  Beckurts  and  Troeger65  found  [«]D  ='—36.17°  in 
a  4.62  p.  c.  chloroformic  solution  and  Deussen66  —36.26°  in  a  3.23 
p.  c.  solution  in  the  same  solvent. 

Grimal  f  prepared  d-cadinene  dihydrobromide,  but  does  not  give 
its  rotatory  power.  M.  p.  124 — 125°. 

Cadinene  dihydr  iodide,  Ci5H24.2HI.  According  to  Wallach67 
this  forms  very  readily  when  the  pure  hydrocarbon,  dissolved  in 

*  Compt.  rend.  135,  pp.  582,  1057. 
so  Ann.,  271.  p.  295. 

61  Ann.,  238,  p.  86. 

62  Arch.  d.  Pharm.,  238,  p.  153. 

63  Arch.  d.  Pharm.,  235,  p.  641. 
6*  Ann.,  252,  p.  151. 

es  Arch.  d.  Pharm.,  236,  p.  398. 

66  Arch.  d.  Pharm.,  238,  p.  153. 

I  Compt.  rend.  135,  pp.  582,  1057. 

67  Ann.,  238,  p.  86, 


56 

several  times  its  volume  of  glacial  acetic  acid,  is  shaken  with  fuming 
hydriodic  acid.  A  heavy  oil  forms  which  soon  crystallizes.  Deussen68 
used  ether  saturated  with  hydriodic  acid.  It  is  best  purified  by 
spreading  on  a  porous  plate  until  thoroughly  dry  and  then  crystal- 
lizing from  a  little  hot  petroleum  ether,  or  ethyl  acetate.  Alcohol 
decomposes  it  readily. 

The  dihydriodide  forms  white  woolly  needles,  melting  at  105—106° 
with  decomposition.     According  to   Wallach  and  Conrady69  [«]D  = 
—48.00°  in  a  5.568  p.  c.  chloroformic  solution. 

Cadi ne ne  nitrosochloride,  CisH^NOCl.  Schreiner  and  Kre- 
mers70  prepare  this  compound  by  dissolving  one  part  of  pure  cadinene 
in  three  parts  of  glacial  acetic  acid  and  one  part  of  ethyl  nitrite, 
then  cooling  this  solution  in  a  freezing  mixture.  To  the  cold  solu- 
tion is  added  very  gradually  one  part  of  a  saturated  solution  of  dry 
hydrochloric  acid  gas  in  glacial  acetic  acid.  The  solution  becomes 
dark  green  and  after  the  addition  of  a  little  alcohol  and  standing 
for  about  two  hours,  the  nitrosochloride  separates  out.  The  com- 
pound is  washed  with  cold  alcohol  and  dried  on  a  porous  plate. 

Cadinene  nitrosochloride  is  a  white  powder  melting  at  98—94° 
with  decomposition. 

Cadinene  nitrosate,  Ci5H24.N204.  According  to  Schreiner 
and  Kremers71  the  nitrosate  is  prepared  as  follows:  One  part  of 
pure  cadinene  is  dissolved  in  three  parts  of  glacial  acetic  acid  and 
one  part  of  ethyl  nitrite.  This  is  then  strongly  cooled  in  a  freezing 
mixture  and  a  solution  of  one  part  of  cone,  nitric  acid  in  one  part 
of  glacial  acetic  acid  gradually  added.  After  standing  a  few  minutes, 
the  turbid  mixture  is  treated  with  an  equal  volume  of  ordinary 
alcohol,  which  will  cause  a  dense  precipitate  of  the  nitrosate.  This 
is  collected,  washed  with  cold  alcohol  and  dried  on  a  porous  plate. 

Cadinene  nitrosate  is  a  light,  white  powder,  sparingly  soluble  in 
cold  alcohol,  more  readily  in  hot  alcohol  and  in  benzol,  but  has  not 
been  recovered  in  a  crystalline  form  from  these  solvents.  It  melts 
between  105  and  110°  with  decomposition. 

Molecular  weight  determinations  by  the  cryoscopic  method,  using 
benzol  as  solvent,  show  it  to  be  a  bisnitroso  compound  (Ci§H24. 
N2Q4)2.72 

68  Arch.  d.  Pharm.,  238,  p.  154. 

69  Ann.,  252,  p.  151. 

70  Pharm.  Archives,  2.  p.  300;   Proc.  Amer.  Pharm.  Assoc.,  47,  p.  181. 

71  Pharm.  Archives,  2,  p.  299:    Proc.  Amer.  Pharm.  Assoc.,  47,  p.  180. 

72  Upjohn,  Thesis  1899,  University  of  Wisconsin. 


57 

Oxygenated  Compounds  Yielding'  Cadinene  or  its  Derivatives. 

Several  sesquiterpene  hydrates  and  other  oxygenated  compounds 
of  high  molecular  weight  are  found  in  volatile  oils  accompanying 
cadinene,  but  whether  all  of  these  will  yield  cadinene  or  its  deriva- 
tives is  still  an  open  question.  In  many  instances  this  appears  not 
to  be  the  case.  So  far  only  one  sesquiterpene  hydrate,  galipol,  and 
another  body  (CioHi60)n,  the  nature  of  which  is  unknown,  have 
definitely  yielded  cadinene  derivatives.  H.  v.  Soden73  and  Rojahn 
are  cf  the  opinion  that  the  alcohol  CisEbaOH  from  West  Indian 
sandalwood  oil  also  yields  cadinene. 

Semmler74  is  of  the  opinion  that  the  high  boiling  blue  fractions 
obtained  in  the  distillation  of  many  oils,  and  variously  designated 
as  coerulin,  azulene,  etc.,  will  yield  cadinene  by  treatment  with  so- 
dium, similar  to  the  reaction  noticed  by  him  for  the  compound 


Oxygenated  compound,  (CioHieOU.  from  asafetida  oil. 
Semmler75  isolated  from  asafetida  oil  a  compound  (CioHi6O)n,  which 
by  repeated  treatment  with  sodium  yielded  a  sesquiterpene,  the 
dihydrochloride  of  which  agreed  in  its  properties  with  cadinene 
dihydrochloride.  This  oxygenated  body  had  the  following  properties: 
b.  p.  133—145°  (9  mm.);  d2o°  =  0.9639;  «„  =  —16°. 

The  properties  of  the  sesquiterpene  obtained  from  it  were:  b.  p. 
123°  (9  mm.);  di5°  s=  0.9241.  The  melting  point  of  the  dihydro- 
chloride was  116°. 

Sesquiterpene  hydrate,  CisEksOH,  from  angostura 
bark  oil.  Galipol.  Beckurts  and  Troeger76  isolated  from  ango- 
stura bark  oil  a  not  well  characterized  sesquiterpene  hydrate,  which 
on  dehydration  gave  a  dextrogyrate  sesquiterpene  yielding  hydro- 
halogen  derivatives  identical  in  all  their  properties  77  with  the  corres- 
ponding cadinene  derivatives.  The  physical  properties  of  galipol 
were  as  follows:  b.  p.  260—270°;  d20°  ==  0.9270;  nu  =1  1.50624; 
optically  inactive. 

The  physical  properties  of  the  sesquiterpene  were:  b.  p.  256  —  260°; 
d2o°  =-  0.9110;  «„  =;  +18°. 

It  may  be  mentioned  that  Beckurts  and  Nehring78  in  1891  found 

73  Pharm.  Ztg.,  45,  p.  878. 

74  Arch.  d.  Pharm.,  229,  p.  20. 

75  Arch.  d.  Pharm.,  229.  p.  15. 

76  Arch.  d.  Pharrn.,  235,  p.  52(5. 

77  Arch.  d.  Pharm.,  236,  p.  397. 

78  Arch.  d.  Pharm..  229,  p.  612. 


58 

that  the  fraction  of  angostura  oil,  boiling  above  240°,  solidified 
when  cooled  in  a  mixture  of  sodium  sulphate  and  hydrochloric  acid. 
This  fraction  must  have  contained  the  galipol,  but  the  later  articles 
of  Beckurts  and  Troeger  make  no  mention  of  this  property  to  so- 
lidify when  cooled. 

Alcohol  CisHssOH,  from  West  Indian  sandalwood  oil. 
In  1900  v.  Soden79  isolated  from  West  Indian  sandalwood  oil  an 
alcohol  for  which  he  proposed  the  name  amyrol.  In  a  later  com- 
munication v.  Soden  and  Rojahn80  report  amyrol  as  consisting  of 
two  alcohols,  the  higher  boiling  one  having  the  composition CisH^oOH, 
and  the  other  CisHysOH.  This  lower  boiling  compound  is  optically 
inactive.  Both  the  alcohols  yield  sesquiterpenes  when  treated  with 
mineral  acids.  The '  sesquiterpene  from  the  lower  boiling  alcohol, 
CisHssOH,  the  authors  suspect  to  be  1-cadinene,  but  they  prepared 
no  derivative  to  confirm  their  belief,  nor  do  they  give  the  properties 
of  the  generated  hydrocarbon. 

5.    Calamene. 

By  boiling  with  sodium,  Kurbatow81  isolated  from  the  high 
boiling  fractions  of  calamus  oil  a  hydrocarbon  Ci5H24,  having  the 
following  properties : 

B.  p.  255-258°;  d0°  =  0.942,  di4°  =  0.9323. 

It  is  described  as  a  colorless,  odorless  oil,  which  would  not  combine 
with  hydrochloric  acid. 

Gladstone82  in  1872  called  this  sesquiterpene  calamene. 

Oil  of  Japanese  calamus  from  Acorns  spuriosus  also  contains  a 
sesquiterpene  which  has  not  been  examined.83 

6.    Caparrapene. 

Tapia84,  in  1898,  isolated  from  caparrapi  oil  an  alcohol  which 
he  recognized  as  a  sesquiterpene  hydrate.  From  this  hydrate,  which 
he  called  caparrapiol,  he  obtained  by  dehydration  the  sesquiterpene 
caparrapene. 


79  Pharm.  Ztj?.,  45,  p.  229. 
so  Pharm.  Ztg.,  45,  p.  878. 
si  Ann..  178,  p.  4. 

82  Pharm.  Journ.,  31,  p.  «87. 

83  Bericht  S.  &  Co.,  April  1889,  p. 7. 
8*  Bull.  Soc.  chim.,  (3),  19,  p.  638. 


59 

Preparation. 

Caparrapiol  is  treated  with  its  own  weight  of  phosphoric  arid 
anhydride.  An  energetic  reaction  takes  place  and  when  this  is  ended, 
the  hydrocarbon  formed  is  distilled  oif  at  ordinary  pressure,  collect- 
ing the  fraction  240 — 250°  separately.  This  fraction  is  again  treated 
with  phosphoric  acid  anhydride  and  rectified.  Tapia  does  not  give 
the  boiling  point  of  this  rectified  product  and  we  must,  therefore, 
conclude  that  he  again  collected  fraction  240—250°. 

The  dehydration  may  also  be  effected  by  heating  the  caparrapiol 
with  twice  its  weight  of  acetic  acid  anhydride  for  two  hours.  The 
oily  liquid,  separated  by  the  addition  of  water,  well  washed  and  dried 
with  anhydrous  sodium  sulphate,  is  distilled  under  diminished  pressure. 

Hydrochloric  acid  and  zinc  chloride  also  remove  water  from 
caparrapiol,  but  besides  caparrapene,  a  large  number  of  polymeric 
substances  are  formed. 

Physical  Properties. 

Caparrapene  is  a  colorless  liquid  which  becomes  yellow  on  ex- 
posure to  air  and  is  less  soluble  in  alcohol  and  glacial  acetic  acid 
than  caparrapiol.  Tapia  found  the  following  physical  constants: 

.     B.  p.  240-260°;   dlfi°  ==  0.9019;   [«]„  =    -2.21°;   n  =  =  1 .495:5. 

Chemical  Properties. 

The  chemical  study  of  caparrapene  is  restricted  to  a  color  reaction 
and  the  preparation  of  a  minute  quantity  of  a  hydrochloride.  The 
color  reaction  consists  in  dissolving  the  sesquiterpene  in  glacial  acetic 
acid  and  adding  a  trace  of  sulphuric  acid.  A  rose  color  develops 
which  passes  into  an  intense  violet. 

Di-hydrochloride.  Tapia  prepared  this  derivative  by  passing 
dry  hydrochloric  acid  gas  into  a  solution  of  caparrapene  in  glacial 
acetic  acid.  The  crude  liquid  hydrochloride,  when  washed  and  dried, 
corresponded  with  the  formula  Cir>H24.2HCl.  After  standing  for 
some  time  small  crystals  separated,  which  were  recrystallized  from 
alcohol.  They  formed. white  hexagonal  plates  which  strongly  polar- 
ize light  and  melt  at  83°.  The  amount  was  unfortunately  too  small 
for  further  study. 

Caparrapiol,  the  sesquiterpene  hydrate  yielding  caparrapene. 
Tapia  separated  the  caparrapiol,  which  is  the  principal  constituent 
of  caparrapi  oil,  by  fractional  distillation  under  diminished  pressure. 


60 

It  is  a  colorless,  mobile  liquid,  having  the  odor  of  the  oil.  It  is 
miscible  with  alcohol,  and  with  a  mixture  of  glacial  acetic  and  sul- 
phuric acids  it  gives  a  red  color.  Dehydrating  agents  give  rise  to  the 
sesquiterpene  caparrapene  described  above. 

Tapia  found  the  following  constants  for  the  impure  caparrapiol 
separated  by  fractional  distillation  from  the  oil : 

B.  p.  180-185°  (40-45  mm.);   di5°  =  0.8915;   [«]„  ==  10.31°; 

n  =z  1.4811. 

The  caparrapene  above  described  was  prepared  from  this  fraction. 

7.    Caryophyllene. 
Synonyms. 

The  class  names  in  the  older  nomenclatures,  such  as, 
Paracopaiba  oil, 
Indifferent  oil  of  cloves, 
Camphene  of  clove  oil,    - 
Paracamphene, 
Cedrene, 
Sesquiterebene, 

Sesquiterebenthene, 
Sesquiterpene, 

Diterpene  (erroneously), 

and  the  specific  names, 

Copaivene, 
Caryophyllene. 

Caryophyllene,  like  cadinene,  is  referred  to  in  the  early  literature, 
before  it  was  characterized,  under  the  general  class  names  of  cam- 
phene,  paracamphene,  sesquiterpene  etc.,  associated  with  the  name 
of  the  oil  in  which  it  occurs,  for  instance,  "Nelken  eamphen"85  (1858). 
It  is  also  called  by  the  name  of  the  oil,  for  instance  "Paracopaivaol"86 


«s  lli-tining.   Ann.,    1(U,   p.    202:    Williams   Canstatts  .Jahresb.  <1.  Pharni..    1858, 
».  1ST. 

so  Posselt,  Ann.,  69,  p.  69. 


61 

(1849),  ''Indifferent  oil  of  cloves" 8?  (1860).  The  sesquiterpene  of 
copaiba  balsam  oil  was  formerly  considered  as  a  diterpene,  because 
its  vapor  density,  determined  by  Dumas'  or  Hoffmann's  method, 
was  found  to  agree  with  the  formula  CooH:{2.  Blanchet88  in  1833 
used  the  term  "salzsaures  Copaivyl"  and  Soubeiran  and  Capitaine89 
in  1839  refer  to  the  sesquiterpene  of  copaiva  oil  as  copaivene. 
Wallach90  in  1892  characterized  the  sesquiterpene  of  clove  oil  and 
proposed  for  it  the  name  of  caryophyllene,  after  the  genus  name  of 
the  plant  yielding-  clove  oil. 

History  and  General  Discussion. 

Caryophyllene  is  perhaps  at  present  the  best  characterized  of  the 
known  sesquiterpenes.  It  appears  to  be  much  less  widely  distributed 
than  cadinene,  but  occurs,  nevertheless,  in  oils  widely  separated 
botanically.  Moreover,  caryophyllene  actually  exists  in  these  oils  as 
such,  whereas  with  cadinene,  as  was  pointed  out,  this  is  a  doubtful 
point. 

The  histoiy  of  caryophyllene  is  closely  connected  with  the  de- 
velopment of  the  chemical  study  of  clove  and  copaiba  balsam  oils. 
The  former  consists  mainly  of  eugenol  and  caryophyllene,  the  latter 
is  said  to  consist  principally  of  this  sesquiterpene.  In  the  preparation 
of  eugenol  from  oil  of  cloves,  the  hydrocarbon  was  usually  obtained 
as  a  side  product,  but  not  closely  studied.  Ettling91  in  1834,  pointed 
out  the  presence  of  a  hydrocarbon  in  clove  oil,  and  since  then,  Bock- 
mann,92  1838,  Bruning,9^  1857,  Williams,94  1858,  and  Church, 9^ 
1875,  have  had  the  hydrocarbon  in  hand,  without,  however,  adding 
anything  to  its  chemical  study,  further  than  to  state  that  no  cry- 
stalline hydrochloride  could  be  obtained. 

As  stated  above,  oil  of  copaiba  balsam  consists  chiefly  of  a  ses- 
quiterpene which  Wallach90  in  1892  identified  as  caryophyllene.  The 


Qmeltn,  Handbook  of  ('hem.,  Engl.  e<l.  4,  14,  p.  2xr». 
Ann.,  7,  p.  15<>. 
Ann.,  34,  p.  i{22. 
Ann  ,  271,  p.  2X7. 
Ann..  <.».  p.  r.x. 


'•»'-'  Ann. 
»«  Ann. 


27,  p.   155. 
104,  p.   202. 


('hern.  <Jaz.,  1858,  p.  170:   Chem    Centralbl.,  21),  p.  4'.»r> 
.Jonrn.  Chein.  Soo.,  28.  p.   1IH 
Ann.,  271  p.  28"». 


62 

results  of  the  earlier  chemical  studies  are  not  wholly  in  agreement 
with  this.  Blanchet97  in  1838  obtained  from  the  oil  a  hydrochloride 
melting  at  54°  and  having  the  composition  CLoHio.  2HC1.  Soubeiran 
and  Capitaine98  in  1840  confirmed  this  formula,  but  gave  the  melting 
point  at  77°.  Later  investigators  failed  to  get  a  hydrochloride  from 
the  oil.  Until  1899  the  dihydrochloride  of  caryophyllene  had  not 
been  prepared  in  a  crystalline  condition,  but  Schreiner  and  Kremers" 
showed,  that  it  could  be  obtained  in  the  form  of  crystals  melting  at 
(i9 — 70°.  Whether  these  ea,rly  investigators  had  this  same  dihydro- 
chloride in  hand  is  very  doubtful  irom  their  analyses,  but  this,  as 
well  as  their  widely  different  melting  points  may  possibly  have  been 
due  to  a  very  impure  condition  of  their  product. 

Another  discrepancy  is  the  fact  that  Strauss100,  Brix1  and  also 
Levy  and  Englander2  found  the  vapor  density  to  agree  with  the 
formula  CaoH32.  This,  however,  may  be  explained  by  the  changes 
which  these  high  boiling  sesquiterpenes  suffer  when  vaporized.  The 
specific  gravity  of  the  fractions  of  copaiba  balsam  oil  as  given  by 
these  investigators  is  usually  somewhat  low  for  caryophyllene,  but 
the  boiling  point,  and  also  the  rotatory  power  when  given,  agree 
fairly  well  with  impure  caryophyllene.  There  are,  however,  a  number 
of  commercial  varieties  of  copaiba  balsam  and  the  widely  varying 
rotatory  power  of  different  samples  of  the  oil,  from  — 7°  to  — 35°, 
would  seem  to  indicate  the  presence  of  other  hydrocarbons  or  possibly 
oxygenated  constituents  in  some  of  these.  This  assumption  would 
explain  many  of  the  discrepancies  mentioned  above,  and  possibly 
also  some  of  the  results  obtained  by  oxidizing  the  oil,  as  will  be 
mentioned  below.  Moreover,  Umney 3  in  1893  failed  to  get  a  hydrate 
from  fraction  264°  of  African  copaiba  oil  by  the  method  used  by 
Wallach  for  caryophyllene.  The  oil,  moreover,  was  dextrogyrate 
20°  42'  while  the  other  varieties  are  laevogyrate.  The  application 
of  the  nitrosite  reaction  of  Schreiner  and  Kremers  to  these  different 
varieties  of  copaiba  oil,  would  no  doubt  clear  up  many  of  these 


97  Ann.,  7.  p.   154. 

98  Journ.  de  Pharm.  26,  p.  565. 

99  Pharm.  Archives,  2,  p.  296;    Proe.  Amer.  Pharin.  Assoc.,  47,  p.  178. 

100  Ann.,  148,  p.  148. 
i  Ber.,  14,  p.  2267. 

9  Ann..  242,  p.  189. 

a  Pharm.  Journ,  58,  p.  215. 


,63 

doubtful  points.  The  blue  nitrosite  and  the  nitrosobenzylamine  de- 
rivatives are  far  better  suited  for  the  detection  and  identification  of 
caryophyllene  than  the  hydrate ;  for  the  failure  to  obtain  the  hydrate~ 
is  not  always  a  good  proof  of  the  absence  of  the  hydrocarbon. 

The  oxidation  products  obtained  from  copaiba  balsam  oil  by  the 
various  workers  also  indicate  that  diffe'rent  hydrocarbons,  or  mix- 
tures of  these  with  other  unknown  compounds  were  present  in  the 
oils  examined. 

In  1892  Wallach  and  Walker4  prepared  from  the  hydrocarbon  of 
clove  and  copaiba  balsam  oil,  a  nitrosochloride  and  the  well  crystal- 
lized hydrate,  alluded  to  above,  by  treatment  with  glacial  acetic 
acid,  sulphuric  acid  and  water.  This  hydrate  when  pure  melted  at 
96°  and  thus  gave  n,  means  for  the  characterization  and  identifica- 
tion of  this  hydrocarbon,  for  which  the  name  of  caryophyllene  was 
proposed.  Later  Wallach5  also  prepared  the  nitrosate  and  nitrol- 
pi  peri  dene  base. 

Schreiner  and  Kremers0  in  1899  still  further  characterized  caryo- 
phyllene by  the  preparation  of  a  crystalline  dihydrochloride,  the  blue 
nitrosite  mentioned  above,  and  two  white  modifications  and  two 
benzylamine  compounds,  so  that  caryophyllene  is  now  the  best  char- 
acterized representative  of  the  group  of  sesquiterpenes. 

Caryophyllene  has  not  been  regenerated  from  any  of  its  deriva- 
tives. Wallach7  attempted  to  regenerate  it  from  the  hydrate,  but 
obtained  an  isomeric  hydrocarbon,  which  he  called  clovene.  Schreiner 
and  Kremers8  attempted  to  regenerate  it  from  the  crystallized  dihy- 
drochloride, but  obtained  a  hydrocarbon  which  differed  decidedly 
from  caryophyllene  in  its  rotatory  power. 

Occurrence. 

The  oils  in  which  caryophyllene  has  been  found  are  by  no  means 
so  numerous  as  those  from  which  cadinene  dihydrochloride  has  been 
obtained.  It  has  been  identified  by  its  hydrate  in  clove,  copaiba 
balsam  and  canella  oils,  and  by  its  blue  nitrosite  in  pepper  oil. 
Other  oils,-  judging  from  the  physical  properties  of  the  sesquiterpene 
contained  in  them,  will  doubtless  be  found  to  contain  caryophyllene. 

In  the  following  classification  the  oils  are  arranged  according  to 


±  Ann.,  271,  p.  285. 

«  Ann.,  279,  p.  391. 

«  Pharni.  Archives,  2,  p.  280,  298. 

^  Ann.,  271,  p.  285. 

8  Pharm.  Archives.,  4.  p.  164. 


64 

the  position  of  the  plants  in  Engler's  Syllabus.  Four  families  and 
four  genera,  are  so  far  included  in  this  list  of  plants  as  yielding 
caryophyllene. 

PIPERACEAK. 

Piper  nigruw.    Black  Pepper  Oil. 

The  first  analyses  of  pepper  oil,  made  by  Dumas9  in  1835,  showed 
it  to  be  almost  free  from  oxygen,  the  results  agreeing  with  the  for- 
mula CsHs.  Eberhardt10  in  1887  verified  these  results.  He  separ- 
ated a  fraction  boiling  between  190—250°  and  a  higher  one  between 
250—310°.  Both  fractions  gave  results  agreeing  with  the  formula 
Ci5H24.  The  fraction  190—250°  had  the  specific  gravity  0.9042  and 
a  specific  rotation  of  — 7°.  No  chemical  work  was  done  on  this 
fraction.  Later,  this  sesquiterpene  is  reported  as  cadinene, n  but 
Schreiner  and  Kremers, 12  suspecting  caryophyllene,  rather  than 
cadinene  from  the  physical  properties  of  the  fraction  obtained  by 
Eberhardt,  made  a  test  for  this  hydrocarbon.  They  obtained  a 
fraction  125—130°  (16  mm.)  which  had  a  specific  gravity  of  0.9058 
and  showed  a  rotation  of  — 7.54°  and  an  index  of  refraction  1.49787. 
These  constants  agree  fairly  well  with  those  of  impure  caryophyllene. 
That  this  hydrocarbon  was  really  under  consideration  was  shown  by 
the  preparation  of  the  characteristic  blue  nitrosite  of  caryophyllene, 
melting  at  113°. 

LEGUM1NOSAE. 

Copaifera  officintilis  and  other  species.    Oil  of  Copaiba. 

Blanchet13  in  1833  distilled  copaiba  balsam  with  water  and  also 
by  itself.  The  oil  obtained  by  distillation  with  water  had  a  sp.  gr. 
of  0.8784  at  22°  and  boiled  at  245°.  Analyses  indicate  the  com- 
position CcHs.  The  oil  obtained  by  direct  distillation  boiled  at  250°, 
otherwise  it  had  the  same  properties  as  the  oil  distilled  with  water 
vapor.  With  hydrochloric  acid  it  yielded  a  hydrochloride,  which, 
when  dissolved  in  ether  and  precipitated  with  alcohol,  melted  at  54° 
and  boiled  at  185°.  Blanchet  determined  the  formula  to  be  CioHie 
2HC1.  Soubeiran  and  Capitaine14  in  1840  found  the  boiling  point  to 
be  260°  and  the  specific  gravity  0.885 ;  the  rotation  of  the  oil  was 
toward  the  left,  somewhat  less  than  French  turpentine.  With  hydro- 


»  Ann.,  1,  p.  159:   comp.  also,  Soubeiran  and  Capitaine,  Ann.,  34,  p.  326. 

10  Arch.  d.  Pharm.,  225,  p.  515. 

11  Ber.  v.  S.  &  Co.,  Oct.  1893,  Suppl.  p.  33;    HeuHlen  Die  Terpene,  p.  175. 

12  Pharm.  Archives,  4*    p.  61;   Proc.  Amer.  Pharm.  Assoc.,  49,  p.  350, 
is  Ann.,  7,  p.  156. 

1*  Ann.,  34,  p.  321, 


65 

chloric  acid  it  yielded  a  hydrochloride  called  by  them  copaiba  cam. 
phor,  after  the  nomenclature  then  in  use.  This  hydrochloride  formed 
short  rectangular  prisms,  odorless  and  transparent,  melting  at  77°. 
It  was  decomposed  by  heat,  and  on  boiling  with  alcohol  an  oil  was 
generated.  They  attempted  to  regenerate  the  hydrocarbon,  which 
they  called  copaivene  by  heating  the  hydrochloride,  but  the  high 
temperature  necessary  also  destroyed  in  part  the  hydrocarbon. 
Analysis  gave  the  same  result  as  found  by  Blanchet,  namely  CioHi«. 
2HC1. 

Posselt15  in  1849  reports  on  the  oil  obtained  from  para  copaiba 
balsam.  It  had  the  formula  CsHg;  sp.  gr.  0.91  and  boiled  at  252°. 
It  absorbed  hydrochloric  acid  gas  readily,  but  gave  no  crystalline 
hydrochloride.  Oxidized  by  heating  with  dilute  nitric  acid  it  yields, 
besides  volatile  acids  not  investigated,  a  resin  and  a  crystalline  acid, 
which  could  not  be  investigated,  as  the  amount  was  too  small. 

Strauss16  in  1868  obtained  from  Maracaibo  copaiba  balsam,  by 
dissolving  the  resin  in  dilute  sodium  hydrate  solution  with  the  aid 
of  heat,  an  oil  floating  on  the  surface  of  the  solution.  This  oil  had 
a  specific  gravity  of  0.921  at  10°  and  boiled  from  250  to  260°.  Its 
composition  was  CsHg,  but  a  vapor  density  determination  agreed 
with  the  formula  C2oHs2  (?).  Oxidation  experiments  led  to  no  de- 
definite  results.  Brix^  hi  1882  ivestigated  fraction  250—260°  of 
Maracaibo  copaiba  balsam  oil.  This  fraction  had  a  specific  gravity 
of  0.892  at  17°,  an  index  of  refraction  of  ]  .503  and  the  molecular 
formula  C2oHs2.  It  yielded  no  crystalline  hydrochloride  and  on  oxi- 
dation with  chromic  acid  mixture,  acetic  and  a  small  amount  of 
terephthalic  acid  resulted.  By  treatment  with  metallic  sodium,  he 
obtained  in  the  last  portions  of  the  distillate  a  dark  blue  oil,  cor- 
responding with  the  improbable  formula  3(C2oH32)-f-H20,  and  called 
by  him  "Copaibaol-Hydrat."  Phosphoric  acid  anhydride  changes 
this  again  to  the  original  sesquiterpene. 

Grimling18  oxidized  the  hydrocarbon  of  copaiba  oil  boiling  at 
252°  with  chromic  acid  mixture  and  obtained  a  crystalline  acid, 
melting  at  207°,  an  indifferent  body,  melting  at  218°,  and  a  small 
amount  of  a  second  acid,  melting  at  170°.  Paracopaiba  balsam  oil 
boiling  at  258°  yielded  oxidation  products  which  differed  from  the 
above.  This  oil  gave  on  oxidation  an  acid  melting  at  136°. 

15  Ann.,  69.  p.  67. 

i«  Ann.,  148,  p.  148. 

17  Monatsh.  f.  Chein.,  2,  p.  507;   Jahresb.  rt.  Pharm.,  1881—82,  p.  214, 

u  Dissertation,  Strassburg,  1879,  p.  2H, 


66 

Levy  and  Englander19  obtained  from  copaiba  oil  a  fraction 
252 — 256°,  which  had  the  composition  OsHg,  and  a  vapor  density 
agreeing  with  C2oHs2,  a  specific  gravity  of  0.8978  at  24°  and  a 
rotation  of  —7°.  On  oxidation  with  chromic  acid  mixture  they  ob- 
tained besides  acetic  acid  an  amorphous  acid,  the  barium  salt  of 
which  indicated  the  formula  Ci^HigOe,  and  a  well  crystallized  acid, 
melting  at  14o°,  which  was  identified  as  a  symmetric  dimethyl 
succinic  acid,  CeHioOi.  The  amount  of  this  acid  was  small,  being 
only  1.5  p.  c.  of  the  oil  used,  and  it  is,  therefore,  doubtful  whether 
this  acid  resulted  from  the  hydrocarbon,  or  from  some  other  unknown 
compound  accompanying  it. 

Wallach20  in  1892  identified  the  sesquiterpene  of  fraction  250— 
270°  from  copaiba  oil  as  caryophyllene  by  preparing  the  character- 
istic hydrate  and  nitrosochloride  of  this  hydrocarbon. 

Umney21  in  1893  examined  African  copaiba  oil,  which  differs  in 
its  physical  properties  fr>  m  the  other  varieties.  He  failed  to  get  a 
crystalline  hydrate  or  hydrochloride  from  fraction  264°.  By  fraction- 
ation  over  metallic  sodium  he  obtained  a  blue  oil  similar  to  that 
obtained  by  Brix  from  the  Maracaibo  variety. 

From  the  foregoing  presentation  of  the  work  done  on  the  various 
copaiba  balsam  oils,  it  will  be  apparent  that  the  reactions  given 
by  the  different  observers  are  somewhat  contradictory,  and  show 
that  caryophyllene  may  not  be  the  only  sesquiterpene  present  in  the 
oil  and  may  even  be  entirely  absent  in  some  of  the  oils,  as  for 
instance,  in  the  African  copaiba  oil  examined  by  Umney.  (See  also 
under  the  section  on  history  and  general  discussion.) 

CANELLACEAE. 
Canella  alba.    Oil  of  Canella. 

Williams22  in  1894  was  able  to  prepare  caryophyllene  hydrate, 
melting  at  92—95°  from  fraction  250—255°  of  canella  oil  by  the 
method  employed  by  Wallach  for  making  caryophyllene  hydrate. 

MYRTACEAE. 
Eugenia  caryophyllata.    Oil  of  Cloves. 

In  1836  Ettling23  obtained  from  oil  of  cloves  by  treating  with 
alkali  and  distilling  with  steam,  a  colorless,  highly  refractive  liquid, 
having  the  specific  gravity  0.918  at  8°.  According  to  Ettling  the 
composition  is  CsHs  and  the  boiling  point  142— 143°. 24  The  oil 
absorbed  hydrochloric  acid  gas  in  large  quantity  but  yielded  no 
crystalline  derivative. 

is  Ann.,  242,  p.  189. 

20  Ann.,  271,  p.  294. 

21  Pharni.  Journ.,  53,  p.  215. 

22  Pharin.  Rundschau,  12,  p.  184. 

23  Ann.,  9,  p.  68. 

2*  A  typographical  error  is  probably  responsible  for  this  extremely  IOAV  boiling 
point.  Church,  however,  also  mentions  that  the  hydrocarbon  distills  at  first  mainly 
between  160 — 165°,  and  that  the  higher  boiling  point  is  reached  only  after  several 
distillations.  On  account  of  this  low  boiling  point  Dumas  [Ann.,  27,  p.  151]  ex- 
pressed the  opinion  that  this  hydrocarbon,  C5H8,  was  probably  identical  with 
turpentine.  It  may  be  that  the  presence  of  a  small  amount  of  water  in  the  oil  was 
responsible  for  the  depression  of  the  boiling  point, 


67 

Bockmann25  in  1838  also  mentions  the  hydrocarbon  which  separ- 
ates on  adding  some  water  to  a  solution  of  oil  of  cloves  in  alkali 
and  heating-.  Briining^6  in  1857  separated  the  hydrocarbon  in  a 
manner  similar  to  that  used  by  Ettling  but  finds  the  boiling  point 
to  be  255°.  Williams27  in  1858  determined  the  boiling  point  at  251° 
and  the  specific  gravity  at  14°  was  0.9016.  Williams  points  out 
that  it  cannot  be  an  isomer  of  turpentine  oil  and  that  it  closely 
resembles  copaiba  and  cubeb  oil,  thus  recognizing  the  sesquiterpene 
nature  of  the  hydrocarbon. 

Church28  in  1875  separated  the  hydrocarbon  from  clove  oil  and 
states  that  during  the  first  distillation  the  oil  came  over  below 
1650,29  the  greater  part  distilling  between  160  and  164°.  The  boiling 
point  of  this  was  raised  to  215—221°  by  a  second  distillation  and 
had  a  specific  gravity  of  0.9064  at  15°.  After  treatment  with  metallic 
sodium  tDe  hydrocarbon  boiled  at  247°  (253.9°  corr.)  and  had  a 
specific  gravity  of  0.905  at  15°,  instead  of  0.9064  as  before.  Analysis 
and  vapor  density  determination  indicated  the  formula  CisH24. 

In  1892  Wallach  and  Walker30  characterized  the  hydrocarbon 
from  clove  oil  arid  gave  it  the  name  of  caryophyllene,  after  the  genus 
name  of  the  plant  yielding  the  oil. 

Eugenia,  caryophyllata.    Oil  of  Clove  Stems. 

Erdmann31  in  1897  obtained  from  the  oil  of  clove  stems,  by 
shaking  out  the  eugenol  with  aqueous  potash,  a  sesquiterpene  boiling 
between  123—125°  (13—14  mm.)  and  having  a  specific  gravity 
0.9050.  While  these  properties  agree  with  caryophyllene,  neverthe- 
less, in  the  absence  of  more  definite  information  concerning  this 
sesquiterpene,  it  cannot  be  definitely  stated  that  it  is  caryophyllene, 
although  it  is  mentioned  as  such  in  several  places. 

Preparation. 

Caryophyllene  has  been  obtained  in  a  fairly  pure  state  from  oil 
of  cloves.  All  the  earlier  investigators  had  the  impure  hydrocarbon 
which  separated  from  the  alkaline  solution  of  clove  oil,  in  hand,  but 
the  later  workers  still  further  purified  this  product  by  distillation 
and  by  chemical  treatment.  All  attempts  to  obtain  it  in  an  absolutely 

25  Ann.,  27,  p.  155. 

26  Ann.,  K)4,  p.  202. 

27  Ann.,  107,  242. 

28  Journ.  Chem.  Soc..  (2)   13,  p.  113. 

29  This  low  boiling  point  may  have  been  due  to  moisture  in  the  oil, 
so  Ann.,  271,  p.  29N. 

8i  Journ,  f,  prakt,  Chem.,  (2)  56,  p,  144, 


68 

pure  form  by  regeneration  from  its  derivatives  as  had  been  done  with 
cadinene  have  so  far  failed;  Wallach  obtained  the  isomeric  clovene 
from  the  hydrate,  and  Schreiner  and  Kremers  obtained  from  the 
dihydrochloride  a  hydrocarbon  which  differed  decidedly  in  its  rotatory 
power  from  caryophyllene. 

Wallach32  in  18 9 2 prepared  caryophyllene  by  fractional  distillation 
of  the  non-eugenol  constituents  of  clove  oil.  He  took  the  fraction 
distilling  between  258—260°.  In  1897  Erdmann33  showed  that  the 
hydrocarbon  thus  prepared  still  contained  some  eugenol  in, the  form 
of  its  acetic  ester.  He  recommended  saponification  with  alcoholic 
potassa  and  then  treating  the  solution  with  water  to  separate  the 
hydrocarbon.  By  distilling  this  hydrocarbon  under  diminished 
pressure  he  obtained  caryophyllene  boiling  at  123—124°  (13  mm.), 
258—259°  (752  mm.),  which  was  free  from  oxygenated  constituents. 

The  caryophyllene  used  by  Schreiner  and  Kremers  34  was  prepared 
on  a  somewhat  larger  scale  in  the  laboratory  of  Fritzsche  Bros,  at 
Garfleld  as  follows: 

Oil  of  cloves  was  treated  in  slight  excess  with  a  7  p.  c.  soda 
solution  at  ordinary  temperature  and  the  solution  extracted  with 
ether.  The  ether  invariably  dissolved  some  of  the  sodium  eugenol . 
The  ethereal  solution  is  evaporated  on  a  water  bath,  at  which 
temperature  any  of  the  aceteugenol  originally  present  in  the  oil  of 
cloves  and  dissolved  by  the  ether,  is  saponified'by  the  sodium  present. 
The  crude  caryophyllene  thus  obtained  was  then  thoroughly  exhausted 
of  any  eugenol  by  repeated  treatment  with  5  p.  c.  soda  solution  and 
then  rectified  by  distillation  with  steam.  This  product  was  found  to 
be  free  from  aceteugenol.  When  distilled  under  20  mm,  pressure 
nearly  all  of  this  oil  came  over  between  136—137°, 

Physical  Properties. 

Caryophyllene  is  .a  colorless,  highly  refractive  liquid,  having  when 
pure,  a  faint  but  pleasant  odor  of  aromatic  woods,  without,  how- 
ever, definitely  suggesting  any  particular  variety.  Its  physical  con- 
stants as  found  by  various  investigators  is  given  in  the  following 
tabulation,  the  arrangement  being  chronological,  giving  at  the  same 
time  the  order  of  purity.  All  these  samples  were  prepared  from  oil  of 
cloves. 


32  Ann.,  271,  p.  298. 

as  Journ.  f.  prakt.  Chem.,  <2)  56,  p.  146, 

8*  Pbarm,  Archives,  2,  p.  273, 


69 

Williams  (1858):  B.  p.  251°;  di4°=0.9016. 

Church  (1875):   B.  p.  253.9°  (corr.);   di5°=0.905. 

Wallach  (1892):  B.  p.  258-260°;  diB°=0;9085.  nD=1.50094; 
optically  active. 

Erdmann  (1897):  B.  p.  123-124°  (13  mm.),  258-259°  (752 
mm.);  do4°=0.9038. 

Schreiner  and  James  (1898):  di>0  =  0.9032:  nD  =  1. 50019; 
[«]„=  -8,74°. 

Schreiner  and  Kremers  (1899);  B.  p.  136-137°  (20mm.);  d200= 
0.9030;  DD=1.49976;  [«]D=  -8.96. 

Schreiner  and  Kremers  also  determined  the  indices  of  refraction 
for  the  three  hydrogen  lines,  the  dispersion  between  the  lines  being 
also  given. 

IL< 1.49694] 

.01136  >| 

H,? 1.50830;  .01834 

I        .00698  J 

Hr 1.51528) 

The  molecular  refraction  agrees  with  two  double  bonds. 
Only  caryophyllene  obtained  from  clove  oil  has  been  considered 
in  the  above  list,  because  even  moderately  pure  samples  of  this 
hydrocarbon  have  not  been  prepared  from  the  other  oils,  and  also 
because  of  the  contradictory  statements  found  for  the  hydrocarbon 
of  copaiba  oil,  which  was  discussed  in  the  historical  part  and  under 
copaiba  oil  in  the  section  on  occurrence, 

Chemical  Properties  and  Derivatives. 

Caryophylleno  yields  with  hydrochloric  acid  a  crystalline  dihydro- 
chloride,  which  is  quite  stable.  Upon  hydration  it  gives  a  mono- 
hydrate,  which  appears  to  be  a  saturated  compound.  It  also  gives 
a  nitrosochloride,  a  nitrosate  and  a  nitrosite.  These  nitroso-comp- 
ounds  and  also  the  hydrate  yield  a  number  of  other  derivatives.  It 
takes  up  four  atoms  of  bromine  but  no  crystalline  bromide  has  been 
obtained. 

For  the  identification  of  caryophyllene,  the  preparation  of  the 
hydrate  has  been  mostly  used.  The  preparation  of  the  hydrate  re- 
quires, however,  quite  a  large  amount  of  the  sesquiterpene  in  a  fairly 
pure  condition,  and  even  then  it  may  happen  that  the  hydrate  is 


70 

not  obtained  in  a  crystalline  form.  A  more  positive  test  is  the 
preparation  of  the  blue  nitrosite  as  described  below,  for  which  only 
a  cubic  centimeter  or  two  of  the  sesquiterpene  fraction  will  be  re- 
quired. The  nitrosite  is  much  more  readily  purified  than  the  hydrate 
and  has  a  sharp  melting  point  as  well  as  other  characteristic  properties. 
In  point  of  time  the  nitrosite  has  a  decided  advantage  over  the 
hydrate  as  a  test  for  identification.  For  further  characterization  the 
hydrate  can  be  changed  to  its  phenyl  urethane  derivative,  and  the 
blue  nitrosite  into  the  nitrolbenzylamine  base,  or  by  light,  into  the 
/3-compound  mentioned  below. 

The  oxidation  experiments  have  nearly  all  been  made  on  copaiba 
oil  and  due  to  the  uncertain  purity  of  the  material  subjected  to 
oxidation,  no  definite  conclusion  can  be  reached.  These  results  have 
already  been  given  under  copaiba  oil  in  the  section  on  occurrence  and 
need  not  be  repeated  here.  It  may  be  mentioned  that  Beckett  and 
Wright,35  by  treating  caryophylleno  from  clove  oil  with  dilute  nitric 
acid,  obtained  neither  toluic  nor  terephthalic  acid.  Attempts  to  get 
cymene  by  treatment  with  bromine  likewise  failed. 

Caryophyllene  dihydrochloride,  CisHoi.SHCl. 

Wallach3(i  in  1892  reports  that  caryophyllene  from  oil  of  cloves 
is  capable  of  adding  hydrochloric  acid,  but  that  the  resulting  comp- 
ound is  liquid.  In  1899  Schreiner  and  Kremers37  succeeded  in  getting 
this  dihydrochloride  in  a  crystalline  condition.  Blanchet38  as  early 
as  1833  and  also  Soubeiran  and  Capitaine39  in  1840,  obtained  from 
copaiba  balsam  oil,  later  shown  by  Wallach  to  contain  caryophyllene, 
a  solid  hydrochloride,  but  it  would  be  unsafe  to  draw  the  conclusion 
that  these  hydrochlorides,  melting  at  54  and  74°,  and  the  analyses  of 
which  agreed  with  the  formula  CioHi6.2H.Cl,  were  identical  with 
caryophyllene  dihydrochloride  Ci5H24-2HCl  melting  at  69—70°. 

Schreiner  and  Kremers40  prepared  the  dihydrochloride  as  follows: 
Caryophyllene  is  dissolved  in  an  equal  volume  of  ether  and  the 
solution  saturated  with  hydrochloric  acid  gas  at  0°.  After  standing 
for  about  24  hours  the  ether  is  allowed  to  evaporate  and  the  heavy 
viscous  oil  mixed  with  alcohol,  in  which  it  is  but  very  sparingly 
soluble  when  cold,  and  this  mixture  exposed  to  a  low  temperature. 

as  Journ.  Chem.  Soc.,  (3)  1 ,  p.  6. 

36  Ann.,  271,  p.  298. 

37  Pharm.  Arch  ,2,  p.  296;  Proc.  Amer,     Phurm.  Asguc.,  47,  p.  178, 

38  Ann.,  7,  p.  154. 

39  Journ.  de  Hharm.,  26,  p.  65, 
*o  I'barm,  Arch.,  2,  p.  2.9S, 


71 

The  undissolved  lower  layer  of  liquid  dihydrochloride  will  soon  solidify 
and  form  a  solid  mass  of  crystals.  These  may  then  be  pressed  on-a- 
porous  plate  to  free  them  from  any  adhering  oily  matter  and  re- 
crystallized  from  a  little  hot  alcohol.  This  should  be  done  quickly, 
a  small  quantity  at  a  time,  as  continued  boiling  with  alcohol  decom- 
poses the  dihydrochloride. 

The  recrystallized  product  occurs  in  fine  white  needles,  melting  at 
69—70°. 

The  dihydrochloride  when  treated  with  glacial  acetic  acid  and 
anhydrous  sodium  acetate,  yields  a  hydrocarbon  which  does  not 
appear  to  be  identical  with  caryophyllene  nor  with  clovene  obtained 
by  Wallach  from  the  hydrate  of  caryophyllene.  Whether  the  re- 
generated oil  is  an  individual  compound  has  not  been  determined, 
but  the  indications  are  that  isomerization  of  the  caryophyllene  has 
taken  place. 

Caryophyllene  nitrosochloride,  CisH^.NOCl. 

Wallach41  in  1892  prepared  some  of  the  nitrosochloride,  but 
complains  of  the  exceedingly  small  yield.  Schreiner  and  Kremers42  in 
1898  found  that  the  action  of  light  had  much  to  do  with  the  form- 
ation of  the  insoluble  white  bisnitroso  compound  from  the  soluble 
blue  compound.  They  prepared  the  nitrosochloride  as  follows :  5  cc. 
of  caryophyllene,  5  cc.  of  alcohol,  5  cc.  of  ethyl  acetate  and  5  cc.  of 
ethyl  nitrite  are  mixed  and  well  cooled  in  a  freezing  mixture.  5  cc. 
of  a  saturated  solution  of  hydrochloric  acid  gas  in  cold  alcohol  are 
then  slowly  added,  continually  rotating  the  flask.  After  allowing  the 
solution  to  stand  for  about  an  hour  in  the  cold,  it  is  exposed  to  the 
light.  The  blue  colpr  soon  fades  away  and  the  nitrosochloride  begins 
to  separate.  The  complete  separation  requires  several  days  or  even 
weeks,  during  which  time  the  solution  is  best  kept  cold,  although  it 
may  be  allowed  to  warm  up  without  any  serious  effect,  as  the 
nitrosochloride  is  fairly  stable,  even  while  in  contact  with  the  mother 
liquor.  The  nitrosochloride  is  collected  and  washed  with  alcohol. 

The  nitrosochloride  thus  obtained  is  a  white  stable  compound 
and  melts  at  158°  with  decomposition.  Wallach  found  the  melting 
point  to  be  161—163°. 

According  to  Schreiner  and  Kremers  the  nitrosochloride  yields  a 
mixture  of  two  nitrol  benzylamine  bases  which  can  be  separated  by 

*i  Ann.,  271,  p.  295. 

«  Pharm.  Arch.,  2,  p.  298. 


72 

crystallization.  They  melt  at  128°  and  1.67°  respectively.  This  may 
indicate  that  the  nitrosochloride  consisted  of  a,  mixture  of  two  isomers. 

The  reaction  with  aniline  has  not  been  fully  studied.  One  sample 
of  freshly  prepared  nitrosochloride  gave  an  energetic  reaction  when 
heated  with  aniline  and  alcohol  the  solution  becoming  of  a  deep 
purple  color,  which  may  have  been  due  to  the  formation  of  amidoazo 
benzene  as  noticed  by  Wallach43  in  the  regeneration  of  pinene  from 
its  nitrosochloride  by  aniline.  No  nitrol  aniline  base  of  caryophyllene 
could  be  obtained  from  the  product  of  the  reaction.  A  second  sample 
of  nitrosochloride,  which  had  been  prepared  a  year  previous,  when 
similarly  treated,  reacted  much  less  violently,  the  product  of  the  re- 
action being  less  deep  in  color,  and  yielding  a  nicely  crystallized 
derivative.44  From  this  it  would  appear  that  under  certain  conditions 
a  nitrol  aniline  base  can  be  obtained  and  under  other  conditions  a 
splitting  off  of  the  nitrosylchloride  takes  place  with  regeneration  of 
a  hydrocarbon.  Perhaps  this  behavior  of  the  nitrosochloride  is  due  to 
varying  proportions  of  the  two  possible  modifications  mentioned 
above.  Further  study  is  necessary  to  decide  these  points  and  if 
found  to  be  true,  it  would  be  of  great  interest  to  prepare  some  of 
the  generated  hydrocarbon  and  study  its  properties. 

A  molecular  weight  determination  shows  the  nitrosochloride  to 
belong  to  the  class  of  bis-nitroso  compounds. 

Caryophyllene  nitrosate,  Cir>H24N204. 

Wallach  and  Tuttle45  in  1894  prepared  the  nitrosate  as  follows: 
10  cc.  of  the  caryophyllene  fraction  of  clove  oil,  9  cc.  of  amyl  nitrite 
and  16  cc.  of  glacial  acetic  acid  are  cooled  to  — 15°  in  a  freezing 
mixture  and  a  similarly  cooled  mixture  of  glacial  acetic  acid  and  cone, 
nitric  acid  is  slowly  added  with  constant  agitation.  The  solution  be- 
comes green  and  a  white  crystalline  precipitate  separates.  As  soon  as 
the  mixture  becomes  dark  green,  some  alcohol  is  added,  and  after  stand- 
ing for  about  two  hours,  the  separated  nitrosate  is  collected  on  a  filter. 

Schreiner  and  Kremers40  proceeded  as  follows:  5  cc.  of  cary- 
ophyllene, 5  cc.  of  glacial  acetic  acid  and  5  cc.  of  ethyl  nitrite,  are 
mixed  and  well  cooled  in  a  freezing  mixture.  A  mixture  of  5  cc.  of 
cone,  nitric  acid  and  5  cc.  of  glacial  acetic  acid  is  then  slowly  added, 
continually  rotating  the  flask.  At  the  end  of  the  reaction  alcohol 

*s  Ann.,  252,  p.  132;   158,  p.  848. 

"  Unpublished  result. 

«  Ann.,  279,  p.  891. 

*«  Pharm,  Arch,,  2,  p,  296;  Proc.  Araer.  Pharm,  AHHOC.,  47,  p,  178, 


73 

is  added  and  after  about  two  hours,  the  separated  nitrosate  is 
collected  on  a  force  filter,  washed  with  cold  alcohol  and  dried  on  a 
porous  plate. 

The  nitrosate  is  insoluble  in  alcohol,  ether,  glacial  acetic  acid, 
but  soluble  in  benzol,  from  which  it  crystallizes  in  fine  transparent 
needles,  melting  at  148 — 149°  with  decomposition. 

Wallach  prepared  from  it  a  nitrol  piperidine  base,  melting  at 
141—143°.  Schreiner  and  Kremers  obtained  a  nitrol  benzylamine 
base  melting  a.t  128°,  identical  with  the  lower  melting  nitrolbenzyl- 
amine  base  obtained  from  the  nitrosochloride. 

Molecular  weight  determinations  show  the  nitrosate  to  be  a  bis- 
nitroso  compound. 

Caryophyllene  nitrosite,  CisHai^Os.  According 
to  Schreiner  and  Kremers47  this  is  prepared  as  follows:  Equal 
parts  of  caryophyllene,  low  boiling  petroleum  ether,  a  saturated 
solution  of  sodium  nitrite  and  lastly  glacial  acetic  acid,  are  mixed, 
continually  agitating  the  solution.  On  adding  the  acid,  the  upper 
petroleum  ether  layer  is  colored  a  beautiful  blue,  which  becomes 
darker  as  more  acid  is  added.  This  solution  is  allowed  to  stand  a 
few  minutes  and  is  then  strongly  cooled  in  ice  water  or  a  freezing 
mixture.  Upon  standing,  or  better  upon  agitation,  the  upper  blue 
layer  solidifies  to  a  mass  of  deep  blue  crystals.  Crystallization 
usually  takes  place  when  so  treated,  but  should  it  fail,  the  merest 
trace  of  solid  nitrosite  brought  in  contact  with  the  cold  solution 
will  cause  it  to  solidify  immediately  to  a  mass  of  crystals.  The 
magma  is  transferred  to  a  force  filter,  first  washed  with  cold  alcohol, 
then  with  water,  and  lastly  with  a  little  more  cold  alcohol,  in  which 
the  nitrosite  is  but  sparingly  soluble.  The  yield  obtained  is  from  12 
to  14  p.  c.  Throughout  this  work  the  solutions  must  not  be  exposed 
to  bright  light  as  the  blue  compound  is  decomposed  by  such  treat- 
ment. 

The  nitrosite  can  be  recrystallized  from  hot  alcohol  in  the  dark, 
in  which  it  is  very  soluble,  but  which  deposits  the  nitrosite  in 
beautiful  deep  blue  needles  on  cooling.  The  melting  point  of  the 
purified  product  is  113°.  It  is  perfectly  stable  up  to  its  melting 
point,  but  when  this  is  reached  a  gas  is  given  off  and  the  liquid  be- 
comes green  and  finally  brown.  The  nitrosite  is  dextrorotatory, 
[a]D  =z  +102.95°  in  a  benzol  solution.  Molecular  weight  determina- 
tions show  it  to  be  monomolecular,  nor  does  it  react  with  benzoyl 

*7    Fharm.  Arch.,  2,  p.  273. 


74 

chloride.    These   facts   indicate   that    in   the   blue  nitrosite  there  is 
present  a  true  nitroso  group. 

The  nitrosite  yields  a  nitrolbenzylamine  base  melting  at  167°, 
which  is  identical  in  its  properties  with  the  higher  melting  nitrol- 
benzylamine base  obtained  from  the  nitrosochloride,  but  different  from 
that  obtained  from  the  nitrosate. 

This  blue  nitrosite  is  very  suitable  for  the  identification  of  cary- 
ophyllene  in  volatile  oils.  It  can  be  prepared  readily  from  fractions 
of  the  proper  boiling  point  and  is  in  every  respect  a  characteristic 
compound  which  can  be  readily  purified.  Only  a  very  small  amount 
of  material  is  necessary  for  this  test,  the  caryophyllene  in  pepper  oil 
having  been  identified  with  2  cc.  of  the  fraction  of  proper  boiling 
point.  For  further  characterization  the  ,?-compound  mentioned  below 
or  the  nitrolbenzylamine  derivative  can  be  prepared  from  it. 

The  nitrosite  is  exceedingly  stable  in  the  dry  form,  but  when 
exposed  to  light  in  a  dissolved  condition  it  readily  decomposes  in 
part  and  suffers  molecular  changes.  This  reaction  takes  place  in  the 
red  end  of  the  spectrum  only  and  differs  somewhat  according  to  the 
solvent  used.  The  two  following  compounds  have  been  obtained  by 
Schreiner  and  Kremers  as  the  result  of  the  action  of  light  on  the 
nitrosite. 

«-C o  m p o un d.  This  was  prepared  as  follows :  5  gr.  of  caryophyl- 
lene nitrosite  were  mixed  with  20  cc.  of  absolute  alcohol  and  exposed 
to  sunlight.  The  blue  crystals  gradually  dissolved  in  the  alcohol  to 
form  a  colorless,  or  only  slightly  yellowish  solution.  Oxides  of 
nitrogen  appear  to  be  given  off  at  the  same  time,  although  this 
could  not  be  definitely  determined.  On  spontaneous  evaporation  an 
oil  remained  from  which  crystals  separated  in  the  form  of  radiating 
needles.  The  yield  of  this  product  is  small,  amounting  to  only  5  p.  c. 
of  the  nitrosite  used. 

This  compound  occurs  in  transparent,  well  developed  crystals, 
melting  at  113—114°.  It  is  readily  soluble  in  alcohol  and  benzol, 
differing  in  this  respect  from  the  /3-compound  described  below.  A 
nitrogen  determination  agrees  with  the  formula  CisH^^Os  and  it 
would,  therefore,  appear  to  be  an  isomer  of  the  blue  nitrosite,  although 
this  is  by  no  means  certain  as  only  a  nitrogen  determination  could 
be  made  with  the  small  amount  of  material  at  hand.  It  is  mono- 
molecular. 


75 

/9-Compound.  This  is  obtained  by  exposing  a  benzol  solution  of 
the  nitrosite  to  sunlight.  The  blue  nitrosite  is  very  soluble  in  benzol 
and  when  this  solution  is  exposed  to  sunlight,  nitrogen  gas  is  given 
off  and  the  blue  solution  decolorizes,  and  solidifies  to  a  mass  of  fine 
white  felt-like  crystals.  The  yield  was  about  12  p.  c.  of  the  blue 
nitrosite  used. 

The  substance  thus  obtained  was  pure  white  and  showed  a  matted 
felt-like  mass  of  crystals  under  the  microscope.  It  differs  in  all  its 
properties  from  those  of  the  a-compound  described  above.  The  melt- 
ing point  of  the  a-compound  is  113—114°;  that  of  the  /5-compound 
146—148°.  The  crystals  are  decidedly  different  in  appearance.  The 
a-conipound  is  readily  soluble  in  both  alcohol  and  benzol,  whereas 
iihe  yj-compound  is  insoluble  in  these  solvents.  It  is  also  insoluble  or 
only  sparingly  soluble  in  ether,  chloroform  and  carbon  disulphide. 
It  is  soluble  in  boiling  ethyl  acetate,  but  cannot  be  recovered  in  a 
crystalline  condition. 

This  /^-compound  reacts  readily  with  benzoyl  chloride  and  also 
with  benzylamine,  but  no  crystalline  compounds  have  so  far  been 
obtained. 

The  exact  nature  of  this  as  well  as  the  ^-compound  can  only  be 
decided  by  further  study. 

Caryophyllene  nitrolbenzylamines,  Ci5H24(NO)NHCH2- 
CeHo.  There  appear  to  be  two  nitrolbenzylamines,  which  differ  from 
each  other  in  crystal  form  and  melting  point.  According  to  Schrei- 
ner  and  Kremers48  caryophyllene  nitrosite  yields  a  nitrolbenzylamine 
base  melting  at  167°  and  the  nitrosate  a  base  melting  at  128°,  while 
the  nitrosochloride  yields  both  these  bases.  For  the  present  these 
bases  have  been  designated  as  a-  and  /3-mtrolbenzylamine  respectively. 

a-Nitrolbenzylamine.  This  compound  was  obtained  as  fol- 
lows: Nitrosite  and  benzylamine  were  heated  together  in  alcoholic 
solution  for  a  short  time.  The  crystals  which  separated  on  cooling 
were  well  washed  with  water  and  recrystallized  from  hot  alcohol. 
The  base  separates  on  cooling  in  pure  white  needles,  melting  at  167°. 
This  nitrolamine  base  obtained  from  the  nitrosite  was  identical  with 
the  first  crop  obtained  from  the  nitrosochloride  as  follows:  The 
product  obtained  by  heating  together  nitrosochloride  and  benzyl- 
amine was  heated  with  alcohol  and  set  aside  to  crystallize.  On  cool- 
ing a  mass  of  fine  needle-shaped  crystals  separated.  These  were 

*s  Pharm.  Arch.,  2,  p.  285. 


76 

collected,  washed  with  alcohol  and  then  with  wa,ter,  to  separate  any 
salts  of  benzylamine.  The  washed  product  was  then  recrystallized 
from  alcohol,  from  which  it  separated  on  cooling  in  pure  white  needles 
of  the  melting  point  167°. 

On  standing,  the  mother  liquor  from  the  crude  base  deposited 
crystals  of  the  /s'-nitrolamine  described  below. 

/2-Nitrolbenzylamine.  This  was  obtained  as  follows:  Cary- 
ophyllene  nitrosate  was  boiled  with  benzylamine  and  alcohol  until 
completely  dissolved.  The  alcoholic  solution  deposited  on  standing, 
nodules  of  crystals  on  the  sides  and  bottom  of  the  dish.  These,  when 
recrystallized  from  alcohol,  again  separated  in  nodules,  and  showed 
a  melting  point  of  128°.  This  nitrolamine-base  is  identical  with  the 
nitrolarnine  obtained  from  the  mother  liquor  of  the  a-nitrolamine 
prepared  from  the  nitrosochloride  as  mentioned  above. 

Caryophyllene  nitrolpiperidine,  Ci5H24  (NO)NHC5Hio. 
Wallach  and  Tuttle49  prepared  this  compound  by  treating  the  nitro- 
sate with  piperidine.  Recrystallized  from  alcohol  it  forms  transparent 
needles  melting  at  141—143°. 

Caryophyllene  hydrate,  CisEbsOH.  Wallaeh  and  Walker50 
employed  the  hydration  method  of  Bertram  for  the  preparation  of 
this  compound.  To  a  mixture  of  1000  gr.  of  glacial  acetic  acid,  20 
gr.  of  cone,  sulphuric  acid  and  40  gr.  of  water,  25  gr.,  or  as  much 
as  will  dissolve,  of  Caryophyllene  are  added,  and  the  solution  heated 
for  about  12  hours  in  a  waterbath.  The  product  of  the  reaction  is 
distilled  with  steam.  Acetic  acid  and  oil  pnss  over  first,  followed  by 
a  less  volatile  oil,  which  soon  solidifies  to  a  crystalline  mass.  To 
free  it  from  adhering  oily  matter,  the  mass  is  strongly  cooled  and 
pressed  on  porous  plates.  When  dry  it  is  best  purified  by  direct 
distillation  from  a  wide  necked  retort  and  subsequent  crystallization 
from  alcohol,  which  raises  the  melting  point  from  94 — 95°  to  96°. 

The  hydrate  boils  constant  without  apparent  decomposition  at 
287 — 289°.  By  applying  heat  slowly  it  can  be  sublimed  in  fine 
glistening  needles.  It  is  almost  insoluble  in  cold  water,  slightly 
soluble  in  hot.  It  is  very  soluble  in  ether,  alcohol,  benzol,  ligroin, 
and  carbon  disulphide.  By  slow  crystallization  from  alcohol  it  forms 
well  developed,  hexagonal,  rhombic  hemihedral  crystals.  The  solid 
compound  is  almost  odorless,  but  the  vapors  have  a  weak  but 
pleasant  odor,  reminding  of  pine  needles. 

49  Ann.,  279.  p.  392, 
so  Ann.,  273,  p.  288. 


77 

The  hydrate  is  optically  inactive  and  is  a  saturated  compound. 
All  of  its  derivatives  are  likewise  saturated.  Caryophyllene  is,  how^ 
ever,  a  hydrocarbon  with  two  double  bonds,  as  is  shown  by  its 
molecular  refraction  and  formation  of  a  dihydrochloride.  It  appears, 
therefore,  that  the  hydration  process  has  changed  the  caryophyllene 
into  an  isorneric  sesquiterpene.  This  is  also  borne  out  by  the  fact 
that  caryophyllene  cannot  be  regenerated  from  the  hydrate.  Dehy- 
dration agents  give  rise  to  an  isomer,  which  has  been  called  clovene 
(see  this).  On  the  other  hand,  the  hydrate  is  not  a  derivative  of 
clovene,  because  this  hydrocarbon  cannot  be  changed  back  into  the 
hydrate  from  which  it  was  generated.  It  seems  therefore  that  the 
hydrate,  while  obtained  from  caryophyllene,  is  not  a  true  derivative 
of  it,  but  of  another  isomeric  sesquifcerpene,  having  only  one  double 
bond,  but  which  does  not  appear  to  be  clovene. 

The  hydrate  also  yields  a  chloride,  bromide,  iodide,  acetate,  and 
nitrate,  none  of  which  have  so  far  been  prepared  from  caryophyllene 
direct  and  appear  to  be  derivatives  of  the  sesquiterpene  which  forms 
the  base  of  the  hydrate,  as  they  are  all  saturated  and  optically  in- 
active compounds. 

Chloride,  CisKbsCl.  Molecular  amounts  of  the  hydrate  and 
phosphorus  pentachloride  are  mixed  in  a  flask  from  which  moist  air 
is  excluded.51  After  a  time  the  mass  heats  up  and  becomes  liquid, 
while  hydrochloric  acid  gas  escapes.  The  phosphorus  oxychloride 
formed  is  distilled  off  in  a  vacuum  and  the  residue,  washed  with  water 
and  dilute  soda  solution,  solidifies  when  cooled.  Recry  stall  ized  from 
alcohol  the  pure  chloride  melts  at  63°  and  distills  without  decompo- 
sition at  293 — 294°.  It  can  also  be  recrystallized  from  ethyl  acetate 
or  ligroin.  The  chloride  is  very  stable;  it  does  not  even  lose  its 
chlorine  by  boiling  for  a  short  time  with  aniline.  It  is  optically  in- 
active. 

Bromide,  CisH^sBr.  Wallach52  prepares  this  as  follows:  10 
gr.  of  the  hydrate  are  warmed  with  a  slight  excess  of  phosphorus 
tribromide.  Hydrobromic  acid  is  given  off.  The  product  of  the 
reaction  is  washed  with  cold  water  and  a  little  ammonia.  The  oil, 
which  at  first  separates  soon  solidifies  to  a  crystalline  mass.  Re- 
crystallized  from  alcohol  it  forms  rhombic  crystals  melting  at  61—62°. 

The  bromide  may  also  be  prepared  as  follows:  To  a  solution  of 

si    Wallach,  Ann.,  271,  p.  289. 
52   Wallach,  Ann.,  271,  p.  290. 


78 

yellow  phosphorus  in  carbon  disulphide,  add  for  each  atom  of  phos- 
phorus three  atoms  of  bromine  and  lastly  one  molecule  of  the  hydrate. 
The  carbon  disulphide  is  removed  by  distillation  and  the  residue 
washed  and  treated  as  mentioned  above.  It  is  optically  inactive. 

Iodide,  CioH25l.  This  is  prepared  by  Wallach53  in  a  manner 
similar  to  that  just  described  for  the  bromide.  To  1  gr.  of  phos- 
phorus dissolved  in  carbon  disulphide  add  the  calculated  amount  of 
iodine  to  form  Pis  and  lastly  15  gr.  of  the  hydrate.  The  carbon 
disulphide  is  distilled  off  and  the  residue  treated  as  with  the  bromide. 

The  iodide  crystallizes  in  long  white  needles  or  rhombic  prisms, 
melting  at  61°.  It  is  decomposed  by  heat  and  is  optically  inactive. 

When  this  iodide  is  treated  in  ethereal  solution  with  metallic 
sodium,  a  hydrocarbon  CsoHso  results.  By  several  crystallizations 
from  ethyl  acetate,  and  lastly  from  absolute  alcohol,  Wallach  and 
Tuttle54  obtained  this  compound  in  large  transparent,  well  developed 
prisms,  melting  at  144—145°.  This  hydrocarbon  is  saturated  and 
is  not  attacked  by  oxidizing  agents,  behaving  in  this  respect  like 
the  paraffins. 

Acetate,  CisHssO.COCHa.  This  compound  is  prepared  by 
Wallach  and  Tuttle  by  digesting  the  iodide  with  sodium  acetate 
and  glacial  acetic  acid  for  several  hours.  The  product  of  the  reaction 
is  distilled  with  steam,  washed  with  dilute  alkali  to  separate  any 
iodine,  and  dried.  On  distilling  it  solidifies  partially,  and  is  purified 
by  expression  and  recrystallization  from  methyl  alcohol.  No  melting 
point  is  given. 

Nitrate,  CisH^sO.NC^.  Wallach  and  Walker55  prepare  this  ester 
as  follows:  Caryophyllene  hydrate  is  liquified  by  a  small  amount  of 
alcohol  and  strongly  cooled.  Fuming  nitric  acid  is  then  added  drop 
by  drop  with  constant  agitation  until  a  strong  excess  of  the  acid  is 
present.  After  several  hours  standing  at  room  temperature,  the 
nitric  acid  ester  crystallizes  out  in  fine,  colorless  needles.  These  are 
filtered  off  and  on  adding  some  water  to  the  filtrate  more  of  the 
ester  separates,  although  somewha/t  sticky.  This  impure  portion  is 
readily  purified  by  distillation  with  steam. 

The  nitrate  is  soluble  in  alcohol,  ether  and  benzol,  but  much  less 
so  in  alcohol  than  the  original  hydrate.  It  crystallizes  in  color- 


53  Ann  ,  271,  p.  290. 
5*  Ann.,  279,  p.  393. 
65  Ann.,  271,  p.  291. 


79 

less  rhombic  prisms  melting:  at  96°.    The  ester  is  saponifiable  only 
with  difficulty  and  is  optically  inactive. 

Urethane,  Cis^sO.CO.NHCeHs.  Wallach  and  Tuttle56  pre- 
pared this  by  warming-  together  in  a  water-bath  molecular  quantities 
of  caryophyllene  hydrate  and  carbanil.  The  urethane  is  separated 
from  the  diphenyl  urea  formed  at  the  same  time  by  crystallization 
from  ether-alcohol.  It  crystallizes  in  needles  melting  at  136—137°. 

8.   Cedrenes. 

The  word  cedrene  was  first  applied  by  Walter57  in  1841  to  the 
hydrocarbon  generated  from  cedar  camphor  (cedrol).  Beckett  and 
Wright58  in  1876  and  Gladstone59  in  1887  applied  the  namo  cedrene 
to  all  members  of  the  CisH^-t  group,  which  accounts  for  the  designa- 
tion cedrene  being  used  by  Muir60  for  the  sesquiterpene  of  sage  oil 
(see  this)  the  properties  of  which  are  quite  different  from  the  cedrene 
of  cedarwood  oil.  Chapman  arid  Burgess,61  Rousset62  and  others 
apply  the  name  to  the  hydrocarbon  found  naturally  in  the  oil.  Wal- 
ter claims  that  these  two  hydrocarbons  are  identical.  The  same  view 
is  expressed  by  Gildemeister  and  Hoffmann,63  but  until  further  evi- 
dence is  forthcoming  they  must  be  considered  as  distinct  sesquiter- 
penes.  In  the  following  the  two  hydrocarbons  will  be  respectively 
referred  to  under  the  names,  natural  cedrene  and  cedrene  from  cedrol. 

History  and  General  Discussion. 

Walter64  in  1841  found  that  when  cedar-wood  oil  was  distilled, 
it  boiled  within  275  and  282°  and  that  the  distillate  solidified  to  a 
mass  of  crystals.  Separating  these  and  recrystallizing  them  from 
alcohol,  he  obtained  the  compound  in  a  purer  form.  From  this  com- 
pound he  obtained,  by  treatment  with  phosphoric  acid  anhydride,  a 
hydrocarbon  which  he  called  cedrene.  Walter  also  obtained  a  hydro- 
carbon directly  from  the  oil.  This  he  considers  as  identical  with 
cedrene  from  cedrol.  Walter  gave  to  the  crystalline  compound 
(cedrol)  the  formula  CieH^-hH^O  and  to  cedrene  the  formula  CieH24. 
In  the  second  article  Walter65  gives  the  composition  as  CieH^sO  and 

56  Ann.,  279,  p.  392. 

57  Ann.,  39,  p.  247. 

ss  Journ.  ('hem.  Soc.,  (3),  1,  p.  G. 

59  Chem.  News,  54,  p.  323. 

eo  Pharm.  Journ.,  37.  p.  994;   Journ.  Chem.  Soc.,  37,  p.  678. 

fii  Proc.  Chem.  Soc.,  No.  168,  p    140;   ('hem.  News,  74,  p.  95. 

62  Bull.  Soc.  Chim.,  (3),  17,  p.  485. 

63  Die  Aeth.  Oele.  p,  357. 
6*  Ann  ,  39,  p.  247. 

65  Ann.,  48,  p.  35. 


80 

CieHae  respectively.  He  also  states  that  the  natural  cedrene,  when 
repeatedly  distilled  from  potassium  has  the  same  properties  as  the 
cedrene  prepared  from  the  crystalline  body  (cedrol). 

Gladstone6'3  in  1871  determined  the  physical  properties  of  cedrene 
obtained  by  the  distillation  of  cedarwood  oil  with  phosphoric  acid 
anhydride.  Chapman  and  Burgess  in  1896  and  Heine  and  Co.67 
distilled  cedrene  directly  from  the  oil  and  determined  its  physical  pro- 
perties. Rousset  in  1897  isolated  cedrene  and  also  the  crystalline 
body,  which  he  calls  cedrol,  from  the  oil.  He  showed  that  cedrene 
was  a  sesquiterpene  and  cedrol  a  sesquiterpene  l^drate.  Rousset 
also  studied  these  compounds  chemically;  from  cedrene  he  prepared 
a  ketone,  cedrone,  by  oxidation,  and  by  reducing  this,  an  alcohol, 
isocedrol. 

Preparation. 

Natural  cedrene.  This  is  prepared  by  separating  it  from  the 
cedrol  in  oil  of  cedarwood  by  distillation,  preferably  in  a  vacuum. 
Since  cedrol  is  not  always  present  in  the  oil,  the  preparation  is  at 
times  very  simple.  The  boiling  point  of  the  hydrocarbon  is  lower 
than  that  of  cedrol. 

Walter88  prepared  the  hydrocarbon  by  repeatedly  distilling  the 
liquid  portions  from  which  he  had  separated  the  cedrol,  collecting 
the  fraction  264 — 268°  and  then  rectifying  this  by  several  distillations 
from  metallic  potassium. 

Chapman  and  Burgess  prepared  cedrene  by  distillation  under 
diminished  pressure  and  Rousset  collected  fraction  125—130°  under 
a  pressure  of  9  mm.  This  fraction  was  further  purified  by  rectifica- 
tion from  sodium. 

Cedrene  from  cedrol.  Walter69  prepared  a  hydrocarbon, 
which  he  called  cedrene  from  the  crystallized  portion  of  cedarwood  oil 
by  treatment  with  phosphoric  acid  anhydride.  The  anhydride  was 
added  in  small  portions  to  the  molten  crystals  and  the  cedrene 
distilled  off.  This  operation  was  repeated  several  times.  Walter70 
found  that  it  could  be  further  purified  by  distillation  from  metallic 
potassium,  until  the  metal  is  no  longer  attacked.  This  latter  treat- 
ment lowers  the  boiling  point  by  more  than  ten  degrees. 

66  .Tourn.  Chem.  Soc.,  (2),  10,  p.  5:   Pharm.  Journ.,  31,  p.  705. 

67  List  of  products  exhibited  at  Paris  1900. 

68  Ann.,  39,  p.  251;   48,  p.  38. 
6»  Ann.,  39,  p.  249. 

TO  Ann.,  48,  p.  36. 


XI 

Rousset71  also  obtained  this  sesquiterpene  by  dehydration  of 
It  also  resulted  together  with  an  acetate  when  cedrol  was 
heated  to  100°  in  sealed  tubes  with  acetic  add  anhydride,  and  on 
oxidizing  cedrol  with  chromic  acid  in  acetic  acid  solution. 

Schirnmel  &  Co.  prepared  cedrene  by  the  action  of  formic  acid 
without  the  application  of  heat. 

Physical  Properties. 

Natural  cedrene  is  a  colorless,  somewhat  viscid  liquid.  The 
properties  of  natural  cedrene  as  found  by  various  investigators  are  as 
follows: 

Walter  (1841):  B.  p.  264—268°;  di4.5°^0.98. 

Walter  (1843):  The  same  properties  as  cedrene  from  cedrol  after 
treatment  with  metallic  potassium. 

Chapman  and  Burgess  (1896):  B.  p.  261—262°;  d15°  =  0.9359; 
[>]„  =  -60°;  riH'/  =  1.4991,  nD  =  1.5015. 

Rousset  (1897):  B.  p.  131-132°  (10  mm.);  «„  =    -47°  54'. 

Heine  &  Co.(  1900) :   B.  p.  261-262°;   di5°  =  0.939;  «„  =  -48°. 

Cedrenefrom  cedrol.  The  properties  found  for  the  hydro- 
carbon prepared  from  cedrol  are  as  follows: 

Walter  (1841):  B.  p.  248°;  di4.5°.- 0.984. 

Walter  (1843):  B.  p.  237°. 

Gladstone  (1871):  B.  p.  252°;  di8°  =  0.9231 ;  nA  =  1.4964. 

Rousset  (1897):  B.  p.  115-117°  (6.5  mm.). 

Schimmel  &  Co.  (1897):  B.  p.  262-263°;  «„  =  -80°. 

Chemical  Properties. 

Natural  cedrene.  Chapman  and  Burgess  state  that  cedrene 
readily  combines  with  hydrochloric  acid  and  with  bromine,  but  that 
no  definite  compounds  could  be  isolated.  Negative  results  were  also 
obtained  in  the  case  of  the  oxides  of  nitrogen  and  nitrosyl  chloride. 
Rousset  obtained  similar  results  with  bromine  and  the  hydrohalogens. 
The  compounds  soon  decomposed,  giving  off  hydrohalogen  and  by 
distillation  in  a  vacuum  the  hydrocarbon  was  again  generated. 

When  cedrene  is  oxydized  with  chromic  acid  in  glacial  acetic  acid 
a  ketone  of  the  formula  CisHW)  results,  which  Rousset  has  called 
cedrone.  This  ketone  boils  at  147—151°  (7.5  mm.),  does  not 
combine  with  sodium  bisulphite,  but  3nelds  iodoform,  which  shows 

7i  Bull.  Soc.  Chim.,  (8),  17,  p.  488. 


82 

that  the  grouping  — CO— CHs  is  present  or  readily  formed.  With 
hydroxylamine  it  yields  an  oxime  boiling  at  175—180°  (8  mm.), 
which,  heated  with  glacial  acetic  acid,  gives  an  acetate  of  the  oxime 
boiling  at  185—190°  (9  mm.). 

The  ketone  yields  by  reduction  with  sodium  an  alcohol,  called 
isocedrol.  It  is  a  very  viscous,  colorless  liquid  boiling  at  148 — 151° 
(7- mm.)  and  corresponding  to  the  formula  Ci5H26O.  Rousset  prepared 
from  this  alcohol  its  benzoic  ester  boiling  at  221—223°  (6  mm.)  and 
having  the  formula  Ci5H25OCO. Cells. 

If  the  oxidation  is  more  violent  than  that  used  for  the  prepara- 
tion of  the  cedrone  a  very  viscous  acid,  boiling  between  220  and  230° 
under  9  mm.  pressure,  and  having  the  formula  Ci2Hi8()3  results. 
The  silver  salt  of  this  acid  has  the  composition  Ci2Hi7O3  Ag.  An- 
other product  of  the  oxidation  is  dimethyl  ketone.  Nitric  acid  pro- 
duces only  resin  acids,  and  alkaline  permanganate  solution  gives  no 
better  results.  Cedrene  cannot  be  hydrated  by  the  action  of  water, 
sulphuric  acid  and  glacial  acetic  acid.  Submitted  to  destructive 
distillation  under  pressure,  there  result  benzene,  toluene,  naphtalene, 
anthracene  and  other  hydrocarbons. 

Cedrene  from  cedrol.  Neither  Walter,  Gladstone  nor  Rousset 
report  any  chemical  work  on  this  sesquiterpene. 

Se  s  q  u  i  t  e  r  p  e  n  e  Hydrate  Yielding  Cedrene.  Cedrol. 
The  alcohol  formerly  known  as  cedar  camphor,  was  separated  by 
Walter  from  the  oil  of  cedarwood  by  expressing  the  semisolid  distil- 
late and  by  recrystallization  from  alcohol  it  was  obtained  in  white 
crystals.  Rousset  isolated  it  from  the  oil  by  fractional  distillation 
under  diminished  pressure  and  then  purifying  the  solidified  distillate 
by  several  recrystallizations  from  methyl  alcohol. 

Cedrol  is,  however,  not  always  a  constituent  of  cedarwood  oil. 
The  readiness  with  which  cedrol  splits  off  water  with  the  production 
of  cedrene,  has  already  been  mentioned.  On  oxidation  cedrol  does 
not  yield  an  aldehyde  or  a  ketone  and  may,  therefore,  be  considered 
as  a  tertiary  alcohol.  By  treatment  with  glacial  acetic  acid  or 
benzoyl  chloride  no  esters  are  produced,  the  hydrocarbon  being 
generated. 

The  physical  properties  of  cedrol  are  as  follows: 

Walter  (1841):  M.  p.  74°;  b.  p.  282°. 

Rousset  (1897):   M.  p.  84°;   optically  active. 


83 

9.    Clovene. 

When  caryophyllene  hydrate  is  treated  with  dehydrating  agents 
a  hydrocarbon  is  generated  which  Wallach  72  has  called  clovene,  after 
clove  oil.  It  is  isomeric  with  caryophyllene  but  contains  only  one 
double  bond,  whereas  caryophyllene  contains  two.73  It  has  not  been 
found  in  nature. 

Preparation.  According  to  Wallach  and  Walker74  clovene  is 
best  prepared  with  the  aid  of  phosphoric  acid  anhydride  as  follows: 
10  gr.  of  caryophyllene  hydrate  are  heated  almost  to  the  boiling 
point  of  the  hydrate  with  an  excess  of  phosphoric  acid  anhydride  for 
fifteen  minutes.  After  cooling,  the  hydrocarbon  is  distilled  off  with 
steam  and  again  treated  with  phosphoric  acid  anhydride  and  then 
rectified  by  distillation. 

Properties.    Clovene  has  the  following  properties: 

B.  p.  261—263°;  dis°  =  0.930;  nD  =  1.50066.  The  molecular 
refraction  found  is  64.77;  calculated  for  Ci^H^F  it  is  64.45. 

Clovene  has  so  far  not  been  changed  back  to  the  crystalline 
hydrate,  nor  has  it  yielded  a  crystalline  nitrosochloride  or  other 

derivative. 

10.  Conimene. 

Stenhouse  and  Groves75  in  1876  obtained  from  conima  resin76 
an  oil  which  boiled  principally  between  260—275°.  By  repeated 
treatment  with  sodium  and  fractionation  they  obtained  a  hydro- 
carbon of  the  formula  Cistbi  boiling  at  264°.  The  name  conimene 
was  given  to  this  sesquiterpene  although  no  chemical  work  or 
determination  of  other  physical  properties  is  reported. 

11.  Cubebene. 

The  name  cubebene  was  formerly  applied  to  cadinene,  which  is  a 
principal  constituent  of  cubeb  oil.  At  present  the  word  cubebene  is 
used  to  designate  the  hydrocarbon  obtained  by  dehydration  from 
cubeb  camphor,  a  sesquiterpene  hydrate  found  in  cubeb  oil.  Cubeb 
camphor  readily  splits  off  water  and  yields  cubebene,  a  liquid  boiling 
between  250— 260°. 77  This  dehydration  takes  place  so  readily  that 

72  Ann.,  271,  p.  294. 

73  For  discussion  see  under  carvopbyllene  hydrate. 
7*  Ann.,  271,  p.  294. 

75  Arn.,  18o,  p.  253;   Journ.  Chem.  Soc.,  1876  (1),  p.  175. 

76  Beilstein  (Vol.  Ill,  p.  538)  includes  icacin,    also  obtained  from  elemi  resin,   in 
the  list  of  nesquiterpenes  by  mistake.     The  composition  of  icacin   is   C46H76O  (Sten- 
house and  Groves,  Ann.,  180,  p.  253)  or  C4.7H78O  (Hesse,  Ann.,  192,  p.  181). 

77  Ber.,  10,  p.  189. 


84 

the  mere  keeping  of  the  hydrate  over  sulphuric  acid  will  cause  a 
partial  dehydration.  Cubebene  has  not  been  prepared  in  a  pure 
condition,  nor  has  it  been  studied  chemically. 

Sesquiterpene  hydrate  yielding  c  u  b  e  b  e  n  e.  Cubeb 
camphor.  *  The  sesquiterpene  hydrate,  called  cubeb  camphor,  is 
found  in  the  oil  distilled  from  old  cubebs.  It  is  not  contained  in  the 
oil  from  fresh  cubebs.78  It  is  obtained  by  exposing  the  oil  to  a  low 
temperature,  and  after  separating  from  the  liquid  portions  of  the 
oil,  it  is  purified  by  recrystallizing  from  alcohol. 

The  compound  was  probably  first  observed  by  Teschemacher 
early  in  the  nineteenth  century.  Later,  it  was  investigated  by  Miil- 
ler7^  (1832),  Blanchet  and  Sell*"  (1833),  Winkled  (1833),  Schmidt 
(1870  and  1877)82  and  Schaer  and  Wyss8^  (1875). 

Cubeb  camphor  crystallizes  in  white,  rhombic  crystals  which 
smell  and  taste  but  slightly  after  cubebs,  having  more  of  a  camphor- 
aceous,  cooling  taste,  than  the  biting  taste  of  cubebs.  It  is  soluble 
in  alcohol,  ether,  carbon  disulphide,  chloroform  and  petroleum  ether. 
It  rotates  the  plane  of  polarized  light  to  the  left. 

The  physical  constants  given  by  various  investigators  are  as 
follows : 

Winkler  (1833) ;  M.  p.  55—56°  R.  (68.7—70°  C.) ;  b.  p.  120—124° 
R.  (150-155°  C.) 

Schmidt  (1870-1877);  M.  p.  65°;  b.  p.  148°. 

Schaer  and  Wyss  (1875);   M.  p.  67°;  b.  p.  148°. 

12.    Galipene. 

The  name  *'galipene"  was  first  applied  by  Beckurts  and  Troeger84 
to  the  dextrogyrate  hydrocarbon  obtained  from  the  alcohol  galipol. 
The  derivatives  of  this  "galipene"85  were  later  shown  to  be  cadinene 
derivatives.86  The  name  of  galipene87  was  then  given  to  the  inactive 
sesquiterpene  isolated  by  fractional  distillation  and  treatment  with 
phosphoric  pentoxide  from  the  oil  of  angostura  bark  by  Beckurts 
and  Troeger.  The  same  inactive  sesquiterpene  could  be  obtained 
from  the  oil  after  it  had  been  treated  with  hydrobromic  acid  for  the 

78  Arch,  d,  Pharm.,  191,  p.  23. 

79  Ann.,  2,  p.  90. 
so  Ann.,  6,  p.  294. 
si  Ann.,  8,  p.  203. 

82  Arch.  d.  Pharm.,  191,  p.  23;  Ber.,  10,  p.  ]xx. 

83  Arch.  d.  Pharm.,  206,  p.  316. 
8*  Arch.  d.  Pharm.,  235,  p.  528. 
85  Arch.  d.  Pharm.,  236,  p.  3i>7. 
ss  See  under  Cadinene. 

87  Arch.  d.  Pharm.,  236,  p.  408. 


85 

preparation  of  the  hydrobromide  of  cadinene.  This  sesquiterpene 
boils  at  255—260°;  d19o  =  0.912;  nD  =  1.50513.  With  hydroehlori_ 
acid  it  forms  liquid  addition  products  which  decompose  readily. 

From  the  method  of  isolation  it  does  not  follow  that  this  in- 
active sesquiterpene  is  really  contained  in  the  oil.  The  action  of  the 
hydrobromic  acid  as  well  as  the  many  distillations  under  ordinary 
pressure  have  doubtless  changed  the  original  oil  to  a  considerable 
extent.88  The  characterization  of  this  sesquiterpene  is  too  indefinite 
to  justify  a  specific  name. 

13      Guajene. 

By  dehydration  of  guajol  from  oil  of  guaiac  wood,  Wallach  and 
Tuttle1  obtained  a  sesquiterpene,  which  has  not  been  identified  with 
any  of  the  known  sesquiterpenes,  but  has  not  been  sufficiently  studied 
to  be  at  all  characterized  as  an  individual. 

Preparation.  These  chemists  prepared  the  hydrocarbon  as 
follows:  10  gr.  of  guajol  were  heated  with  an  excess  of  zinc  chloride 
to  180°  for  about  an  hour.  The  colored  product  of  the  reaction  was 
then  distilled  with  steam.  The  blue  oil  obtained  was  dried  with  solid 
caustic  alkali  and  distilled  in  a  vacuum.  The  fraction  boiling  at 
124—132°  (13  mm.)  was  collected,  but  analysis  showed  that  the 
hydrocarbon  was  not  quite  pure. 

Properties.  The  fraction  thus  obtained  is  blue,  but  it  must 
not  be  assumed  that  this  is  necessarily  due  to  the  hydrocarbon. 
The  production  of  small  amounts  of  oxygenated  compounds  from 
the  readily  oxidized  sesquiterpene  are  probably  responsible  for  the 
coloration.  According  to  Wallach  and  Tuttle  this  blue  color  dis- 
appears when  the  hydrocarbon  is  kept  for  some  time  in  contact  with 
metallic  sodium. 

The  sesquiterpene  has  the  following  physical  constants: 

B.  p.  124—128°  (13  mm.);   d2<>°  =  0.910;   n,,  =  1.50114. 

No  chemical  work  is  reported. 

Sesquiterpene  hydrate  yielding  g  u  a  j  e  n  e.  Guajol. 
Schimmel  and  Co.  2  obtained  as  the  principal  constituent  an  alcohol 
from  guaiac  wood  oil.  As  the  latter  has  erroneously  been  brought 
into  commerce  as  champaca  wood  oil,  the  alcohol  has  also  been 
designated  as  champacol.3  The  compound  was  more  closely  studied 
by  Wallach  and  Tuttle4  in  1894. 

88  See  under  Cadinene. 

*  Continued  from  Pharin.  Archives,  vol.  6,  p.  141.  « 

1  Ann.,  279,  -p.  396. 

2  Ber.  v.  S.  &  C.,  April  1892,  p.  42. 

3  Merck  &  Co.     Geschaftsbericht,   Jan.  1.    1898;   Chein .    Ztg.    Repert.,  17,    p.  31; 
Ber.  v.  S.  &  Co.,  April  1893,  p.  33 ;   Ann.,  279,  p.  :•?'.»."). 

*  Ann.,  279,  p.  395. 


86 

Preparation.  Shortly  after  distillation  the  viscous  guaiac 
wood  oil  will  solidify  completely  to  a  mass  of  crystals  of  guajol. 
Wallach  and  Tuttle  purified  the  crude  alcohol  as  follows:  The  crude 
material  was  first  distilled  in  a  vaccuum.  The  yellowish  syrupy 
portion  collected  at  155—165°  (13  mm.)  soon  solidified.  The 
crystalline  mass  was  mixed  with  ether  to  form  a  thick  paste  which 
was. spread  on  porous  plates.  By  recrystallizing  from  alcohol  the 
guajol  could  be  obtained  in  a  pure  condition.  Analysis  showed  it  to 
be  a  sesquiterpene  hydrate. 

Properties.  Guajol  crystallizes  readily  in  large,  well  developed, 
transparent  prisms.  When  pure  it  shows  the  following  properties: 

Schimmel  &  Co.:  M.  p.  91°;  b.  p.  148°  (10  mm.)  laevogyrate. 

Wallach  and  Tuttle:  M.  p.  91°;  b.  p.  288°. 

Especially  characteristic  for  guajol  are  the  brilliant  color  changes 
which  are  produced  by  dehydrating  agents.  Dilute  sulphuric  acid, 
which  acts  readily  on  patchouly  alcohol,  does  not  act  on  guajol,  but 
phosphoric  pentoxide  abstracts  water  at  a  high  temperature,  devel- 
oping a  deep  red  color,  and  giving  rise  to  a  hydrocarbon  and  much 
resinous  material.  The  same  reaction  takes  place,  but  with  better 
results,  when  chloride  of  zinc  is  employed  as  has  been  described  above. 

According  to  Schimmel  &  Co.5  guajol  yields  with  acetic  acid 
anhydride  a  liquid  acetic  ester,  boiling  at  155°  (10  mm.).  Guajol  can 
be  regenerated  from  it  by  saponification. 

14.    Gurjunene. 

Werner1  in  1862  examined  oil  of  gurjun  balsam  and  found  it  to 
consist  principally  of  a  hydrocarbon  C2oHs2,  boiling  at  255°,  having 
a  specific  gravity  of  0.9044  at  15°  and  a  rotation  of  —10°.  Two 
vapor  density  determinations  made  by  Kohlrausch2  in  1879  show 
the  formula  to  be  that  of  a  sesquiterpene,  CisH^.  According  to 
Fliickiger  it  absorbs  hydrochloric  acid  but  yields  no  crystalline 
hydrochloride.  The  chemical  work  done  on  this  sesquiterpene  is 
restricted  almost  entirely  to  color  reactions  when  treated  with  acids. 
Fliickiger  gives  the  following  test  for  the  identification  of  gurjun 
balsam  oil.  The  oil  when  dissolved  in  about  twenty  times  its  weight 


s  Ber.  v.  S.  &  Co.,  April  1892,  p.  42. 

1  Ztsch.  f.  Chern.,  5,  p.  588;  Jahresb.  d.  Pharm.,  18CJS,  p.  ."><). 

2  Fliickiger,  Pharmacognosie,  3rd  ed..  p.  102. 


87 

of  carbon  disulphide  gives  with  a  drop  of  a  cold  mixture  of  equal  pans 
of  sulphuric  and  nitric  acids  (1.180)  a  bright  red  color  which 
gradually  changes  to  violet. 

Although  gurjun  balsam  oil  consists  almost  wholly  of  sesquiter- 
penes  it  is  by  no  means  certain  that  only  one  sesquiterpene  is  present. 
The  widely  varying  rotatory  powers  of  different  samples  of  oil,  from 
«D  =  _35°  to  —130°  indicate  that  the  oil  may  not  be  a  chemical 
unit.  In  one  case3  the  rotation  was  even  strongly  to  the  right. 

Without  characterizing  the  sesquiterpene,  Heine  &  Co.4  gave  it 
the  name  of  gurjunene.  The  product  made  by  them  had  the  follow- 
ing properties: 

B.  p.  (?);  di5°  =  0.920;   «D=— 136°. 

See  also  Sesquiterpene  from  Minjak  Lagam  Balsam  Oil. 

15.    Heveene. 

Heveene1  is  obtained  by  the  destructive  distillation  of  cautchouc 
and  is  but  little  investigated.  Beilstein2  includes  it  among  the  ses- 
quiterpenes,  giving  its  boiling  point  as  255 — 265°.  It. absorbs  hydro- 
chloric acid  gas,  forming  .  a  hydrochloride  corresponding  to  the 
formula  CisH^HCl,  but  this  compound  does  not  crystallize  and 
decomposes  readily. 

16.    Humulene. 
Synonyms. 

Diterpene  (erroneously). 

Terpene  of  poplar  bud  oil. 

Humulene. 

Based  on  a  Vapor  density  determination  Piccard1  in  1874  called 
the  hydrocarbon  of  poplar  bud  oil  a  diterpene.  In  1899  Fichter  and 
Katz, 2  who  identified  the  hydrocarbon  as  humulene  also  speak  of  it 
as  the  terpene  of  poplar  bud  oil.  The  name  humulene  was  given  to 
the  charactized  sesquiterpene  by  Chapman3  in  1895,  after  the  name 
of  the  plant,  Hnmulus  lupulus,  yielding  the  oil  in  which  it  was  first 
found. 


3  Dymock,  Warden  and  Hooper,  Pharmacographia  Indica,  1890,  I,  p.  193. 
*  List  of  products  exhibited  at  Paris,  1900. 

1  This  name  was  given  to   the  hydrocarbon  by  Bouchardat   (Journ.  d.  Phann., 
1837,  p.  454;   Ann.,  27.  p.  35)  from  Heveti  ffiiianensis,  yielding  cautchouc. 

2  Handb.  d.  org.  Chera.,  Ill,  p.  538. 

1  Ber.,  7,  p.  1486. 

2  Ber.,  32,  p.  3183. 

3  Journ.  Chem.  Soc.,  (57,  p.  54. 


88 

History  and  General  Discussion. 

In  1895  Chapman4  isolated  from  oil  of  hops,  a  sesquiterpene 
which  differed  in  its  physical  properties  from  any  of  the  known 
sesquiterpenes,  although  in  some  respects  its  derivatives  resembled 
the  corresponding  compounds  of  caryophyllene  as  far  as  then  known. 
This  sesquiterpene  Chapman  calls  humulene.  In  1899  Fichter  and 
Katz  obtained  this  same  hydrocarbon  from  the  oil  of  poplar  buds. 

The  further  characterization  of  caryophyllene  by  Schreiner  & 
Kremers5  shows  conclusively  that  humulene  is  quite  distinct  from 
caryophyllene.  Chapman's  humulene  nitrosochloride  melted  at  164 
to  165°  and  caryophyllene  nitrosochloride  at  161—163°  as  reported 
by  Wallach.  This  led  Chapman  to  think  that  the  two  compounds 
might  be  identical,  but  he  could  not  obtain  a  hydrate  from  his 
sesquiterpene  under  the  same  conditions  that  caryophyllene  readily 
yielded  this  compound.  As  no  other  compounds  of  caryophyllene  were 
known  at  that  time,  further  comparisons  could  not  be  made.  With 
other  known  compounds  now  at  command  a  comparison  shows  that 
the  two  sesquiterpenes  cannot  be  identical,  although  the  great  simi- 
larity in  their  chemical  behavior  is  striking.  Both  yield  all  three 
nitroso  derivatives.  Moreover,  the  nitrosite  in  each  case  is  blue  and 
yields  an  isomeric  white  variety.  In  the  case  of  caryophyllene  this 
white  compound  is  obtained  by  the  action  of  light,  whereas  the  white 
humulene  iso-nitrosite  was  obtained  by  repeated  crystallizations  or 
by  heating  for  some  time  with  alcohol.  Even  with  humulene  the 
change  is  possibly  due  more  to  the  action  of  light  during  the  process 
of  recrystallization  and  boiling,  than  to  the  action  of  the  alcohol. 
The  great  similarity  in  the  behavior  of  the  two  compounds  makes  it 
highly  probable  that  the  blue  humulene  compound  win1  react  similarly 
on  exposure  to  light  as  does  the  caryophyllene  derivative.  Whether 
or  not  a  /9-compound  can  be  obtained  from  humulene  as  from  cary- 
ophyllene by  exposing  a  benzol  solution  of  the  nitrosite  to  light, 
experiment  alone  can  decide. 

A  further  apparent  analogy  between  the  two  hydrocarbons  was 
that  both  yielded  only  liquid  addition  products  with  hydrochloric 
acid,  but  this  no  longer  holds,  since  the  caryophyllene  compound  has 
been  obtained  in  a  crystalline  form.  However,  it  is  also  probable 
that  a  crystalline  humulene  dihydrochloride  is  obtainable  in  a 


*  Journ.  Chem.  Soc.,  67,  pp.  54,  780. 
5  Pharm.  Archives,  1,  p.  209  et  seq. 


so 

manner  similar  to  that  by  which  the   caryophyllene  derivative  was 
prepared. 

The  derivatives  of  the  two  hydrocarbons,  although  so  similar, 
show  by  their  melting  points  that  they  cannot  be  identical.  The 
melting  points  of  the  nitrosochlorides,  a,s  in  the  case  of  the  terpenes, 
cannot  be  used,  as  it  is  rather  a  decomposition  point  than  a  melting 
point;  but  the  melting  points  of  the  other  compounds,  especially  of 
the  nitrosite  and  its  derivatives,  are  characteristic.  Caryophyllene 
nitrosite  melts  at  113°,  whereas  the  corresponding  humulene  deriva- 
tive melts  at  120—121°;  the  white  compound  from  caryophyllene 
nitrosite  melts  at  112—114°,  humulene  iso-nitrosite  at  165—168°. 
The  nitrolbenzylamine  bases  show  still  more  conclusively  the  differ- 
ences between  these  hydrocarbons.  The  base  obtained  from  the 
nitrosochloride  melts  in  the  case  of  the  caryophyllene  compound  at 
167°,  in  the  case  of  the  humulene  compound  at  136°.  Moreover. 
Chapman  obtained  the  same  piperidine  base  from  both  the  nitrosate 
and  nitrosochloride,  whereas  caryophyllene  nitrosate  and  nitroso- 
chloride yield  different  compounds  with  berizylamine. 

Occurrence. 

Humulene  is  not  widely  distributed.  It  has  been  found  in  only 
two  oils,  but  these  come  from  plants  belonging  to  different  families. 
It  is  not  improbable  that  with  further  study  humulene  will  be  found 
in  other  oils  as  well. 

Salicacejv. 

Populus  nigra.    Oil  of  Poplar  Buds. 

Piccard6  in  1873  found  oil  of  poplar  buds  to  boil  principally 
between  260  and  261°  and  to  correspond  to  the  formula  (CsHs). 
Its  specific  gravity  was  0.9002.  An  analysis  of  a  sample  of  oil  which 
had  stood  for  several  weeks  showed  it  to  contain  3.48  p.  c.  of  oxygen. 
In  a  later  communication7  he  reports  the  hydrocarbon  as  a  diterpene 
C2oHs2,  drawing;  his  conclusion  from  a  vapor  density  determination 
by  Dumas'  method,  which  would,  of  course,  give  too  high  a  result 
with  compounds  of  this  nature.  The  fraction  had  a  rotation  of 
+  1.9°  in  a  100  mm.  tube. 

In  1899  Fichter  and  Katz8  examined  the  sesquiterpene  from  oil 
of  poplar  buds.  They  obtained  a  fraction  132—137°  (13  mm.), 

e  Ber.,  6,  p.  890. 
7  Ber.,  7,  p.  1486. 
s  Ber.,  32,  p.  3188. 


90 

263—269°  (760  mm.)  having  the  specific  gravity  0.8926  and  a 
rotation  of  -J-  10°  48'  in  a  200  mm.  tube.  Although  the  constants 
of  this  fraction  do  not  agree  with  those  of  humulene  as  found  by 
Chapman,  the  preparation  of  characteristic  derivatives  showed  that 
it  contained  humulene.  The  authors  are  of  the  opinion  that  a  second 
sesquiterpene  accompanies  the  humulene  in  poplar  bud  oil. 

The  humulene  was  identified  by  the  preparation  of  a  nitroso- 
chloride,  m.  p.  164—170°;  a  blue  and  a  white  nitrosite,  m.  p.  127 
and  172°  respectively;  a  nitrosate,  m.  p.  162—163°,  a  nitrolpiper- 
idine  and  a  nitrolbenzylamine  base  and  their  hydrochlorides. 

Moraceae. 

Humulus  lupulus.    Oil  of  Hops. 

In  1893  Chapman9  described  a  sesquiterpene  obtained  by 
fractional  distillation  from  oil  of  hops.  In  1895  this  was  followed  by 
two  moro  articles  in  which  the  sesquiterpene  was  characterized  by  the 
preparation  of  several  characteristic  derivatives.  Fraction  168—173° 
(60  mm.),  constituting  nearly  two  thirds  of  the  oil  used,  was  purified 
by  boiling  with  sodium  under  diminished  pressure  and  rectified  by 
distillation.  The v  sesquiterpene  thus  obtained  Chapman  called  hum- 
ulene because  it  differed  in  its  properties  from  any  of  the  known 
sesquiterpenes.  The  first  of  the  articles  mentioned  is  on  oil  of  hops, 
but  includes  the  preparation  of  humulene  nitrosochloride  by  conduct- 
ing nitrosyl  chloride  into  a  chloroformic  solution  of  the  sesquiterpene, 
as  well  as  the  preparation  of  the  piperidine  nitrolamine  base  from 
the  nitrosochloride.  Attempts  to  prepare  a  crystalline  bromide  or 
hydrochloride  proved  fruitless.  The  second  Article  is  on  humulene 
derivatives  in  particular  and  includes  the  preparation  of  the  nitrosate, 
isonitrosite,  nitrolbenzylamine  base  and  the  hydrcchloride  of  this  as 
well  as  of  the  nitrolpiperidine  base. 

Preparation. 

Humulene,  like  caryophyllene,  has  not  been  obtained  in  a  pure 
state  by  regeneration  from  any  of  its  derivatives.  It  is  prepared  by 
fractional  distillation  from  oil  of  hops.  Chapman11  collected  fraction 
168—173°  (60  mm.),  corresponding  to  256—261°  (760  mm.).  This 
fraction  was  purified  by  repeated  distillation  over  sodium  under 
diminished  pressure,  until  the  metal  remained  bright.  Thus  purified 

9  Proc.  Chem.  Soc.,  1S93,  p.  177. 

10  Journ.  Chem.  Soc..  67,  pp.  54,  780. 

11  Journ.  Chem.  Soc.,  67,  p.  59. 


91 

it  boiled  at  166—170°  (60  mm.)   and  the  analysis  showed  it  to  be 
free  from  oxygenated  compounds. 

Physical  Properties. 

Of  the  physical  constants  given,  only  those  of  Chapman  can  be 
considered  as  characteristic  of  the  pure  hydrocarbon.  The  results  of 
Piccard  and  of  Fichter  and  Katz  apply  to  crude  humulene  fractions. 
Even  the  slight  rotatory  power  noticed  by  Chapman  is  probably  due 
to  a  trace  of  an  active  substance  accompanying  the  humulene,  as 
another  sample,  prepared  from  the  same  source  in  the  same  manner, 
had  a  somewhat  greater  rotatory  power.  Humulene  may,  therefore, 
be  considered  as  being  inactive  when  perfectly  pure.  The  physical 
constants  found  were: 

Piccard  (1873):  B.  p.  260-261°;  d  =  0.9002;  aD  =  +1.9°. 

Chapman  (1898):   B.  p.  261—265°  (corr.);  d!i!  =  0.8987;    d?£= 

15f  20° 

0.8955;  [«]D  =  +1.2°;   nHa  =  1.4978. 

Chapman  (1895):  B.  p.  166-170°  (60mm.),  263-266°  (760 
mm.);  d«!  =  0.9001,  d?o!  =  0.8977;  aD  =  -0.5°;  nD=1.5021,  vtta  = 

15°  200 

1.4978. 

Fichter  and  Katz  (1899):  B.  p.  132—137°  (13  mm.);   263—269° 

(760mm.);  d«!  =  0.8926 ;   OD=  +5°  24'.i2 

40 

The  molecular  refraction  calculated  from  the  index  of  refraction 
shows  humulene  to  have  two  double  bonds.  This  is  also  indicated 
by  the  bromine  absorption  and  by  the  preparation  of  a  liquid 
dihydrochloride. 

Chemical  Properties  and  Derivatives. 

Humulene,  having  two  double  bonds,  is  capable  of  forming  a 
tetrabromide  and  dihydrochloride  or  dihydrobromide,  but  none  of 
these  has  been  obtained  in  a  pure  or  crystalline  condition.  It  also 
yields  a  nitrosochloride,  a  nitrosate  and  two  nitrosites,  the  one  blue, 
the  other  white,  as  well  as  nitrolamine  bases,  derived  from  these. 
Nitrosohumulene,  which  on  reduction  yields  a  base,  has  been  pre- 
pared, but  neither  of  these  compounds  has  been  obtained  in  a  pure 
and  crystalline  condition.  By  means  of  all  these  derivatives,  humu- 
lene is  definitely  characterized.  The  compound  best  suited  for  iden- 
tification, however,  is  the  blue  nitrosite.  From  this  the  white  iso- 

12  According  to  F.  and  K.  this  rotation  is  due  to  the  presence  of  a  second 
sesquiterpene. 


92 

nitrosite  can  be  prepared  and  probably  also  the  nitrol  bases  although 
Chapman  and  also  Fichter  and  Katz  prepared  these  from  the  nitroso- 
chloride. 

Humulene  readily  absorbs  oxygen  as  was  shown  by  Piccard, 13 
who  analysed  the  hydrocarbon  after  standing  a  few  weeks  and  found 
it  to  contain  3.48  p.  c.  of  oxygen.  Oxidation  with  cold  aqueous 
potassium  permanganate  gave,  according  to  Chapman, 14  carbonic 
and  acetic  acids,  together  with  a  non-volatile  acid  which  was  not 
identified.  When  treated  according  to  the  hydration  method  used 
by  Wallach  for  caryophyllene,  no  crystalline  hydrate  could  be  ob- 
tained. 

Humulene  dihydrochloride,  CisH^HCl.  Chapman15  pre- 
pared a  liquid  dihydrochloride  by  passing  dry  hydrochloric  acid  gas 
into  a  well  cooled  solution  of  humulene  in  four  times  its  volume  of 
ether.  On  evaporation  of  the  ether  a  yellow  oil  was  left,  which  when 
purified  by  washing  with  cold  alcohol  and  drying,  gave  on  analysis 
a  result  agreeing  with  the  formula  CisH^s.SHCl.  Attempts  to  obtain 
it  in  a  crystalline  condition  failed,  nor  could  it  be  purified  by  distill- 
ation under  diminished  pressure  without  the  loss  of  large  amounts 
of  hydrochloric  acid  gas.  The  specific  gravity  of  the  impure  liquid 
dihydrochloride  was  1.063. 

Humulene  n it roso chloride.  Ci5H24NOCl.  Chapman16  pre- 
pared this  compound  by  passing  nitrosyl  chloride  slowly  into  a  well 
cooled  solution  of  one  volume  of  humulene  in  three  volumes  of  chloro- 
form. After  a  time  a  white  crystalline,  substance  separated,  the 
amount  of  which  was  increased  by  adding  cold  alcohol.  The  precipi- 
tate was  collected  on  a  filter,  washed  with  cold  alcohol,  and  dried  in 
a  vacuum  over  sulphuric  acid.  It  is  fairly  soluble  in  chloroform  and 
can  be  obtained  from  this  solution  in  a  more  distinct  crystalline 
condition  by  the  addition  of  alcohol. 

Fichter  and  Katz17  prepared  the  nitrosochloride'by  treating  the 
humulene  fraction  with  amyl  nitrite  or  ethyl  nitrite  and  hydrochloric 
acid  and  recrystallized  it  from  benzol  or  chloroform  with  the  addition 
of  methyl  alcohol. 

The  nitrosochloride  is  a  white  finely  crystalline  substance  and  is 
comparatively  stable.  It  melts  at  164—165°  (Chapman)..  164—170° 

is  Ber.,  6.  p.  890. 

i*  Journ.  Chem.  Soc.,  67,  p.  61. 

is  Journ.  Chem.  Soc.,  67,  p.  61. 

16  Journ.  Chem.  Soc.,   67,  p.  789  et  «eq. 

IT  Ber.,  32,  p.  3184. 


(Fichter  and  Katz)  with  decomposition.  With  organic  bases  it  yields 
nitrolamine  compounds.  Treatment  with  sodium  ethylate  changes  it 
to  nitrosohumulene. 

Humulene  nitrosate,  CisH^.^O*.  Chapman18  prepared 
this  as  follows:  A  mixture  of  5  volumes  of  humulene,  5  volumes  of 
amyl  nitrite  and  8  volumes  of  glacial  acetic  acid  was  cooled  in  a 
freezing  mixture  to  about  —15°.  To  this  solution,  a  well  cooled 
mixture  of  equal  volumes  of  nitric  acid  and  glacial  acetic  acid  was 
added  little  by  little,  with  constant  shaking.  A  white  crystalline 
substance  soon  formed,  the  mixture  becoming  almost  solid.  Alcohol 
was  now  added  and  after  standing  in  the  cold  for  about  an  hour, 
the  nitrosate  was  collected  on  a  force  filter  and  washed  with  cold 
alcohol.  It  was  purified  by  recrystallization  from  hot  benzol. 

The  nitrosate  is  obtained  in  extremely  fine,  colorless  needles, 
often  forming  rosettes.  It  is  practically  insoluble  in  alcohol  and  in 
ether,  but  fairly  readily  soluble  in  benzol,  chloroform,  and  glacial 
acetic  acid  on  warming.  The  purified  nitrosate  melts  at  162 — 163° 
with  decomposition. 

Humulene  nitrosite,  CisHo^.^Oa.  Cha.p man 19  prepared  this 
compound  by  adding  to  a  well  cooled  mixture  of  equal  volumes  of 
humulene  and  light  petroleum  ether,  a  cone,  aqueous  solution  of 
sodium  nitrite,  and  lastly  a  volume  of  acetic  acid  equal  to  that  of 
the  humulene  taken,  little  by  little,  with  frequent  shaking.  From  the 
upper  hydrocarbon  layer  deep  blue  needles  soon  separated,  which, 
after  some  hours,  were  collected  and  purified  by  one  recrystallization 
from  boiling  alcohol. 

The  nitrosite  crystallizes  in  magnificent  blue  needles  melting  at 
about  120°  (Chapman),  127°  (Fichter  and  Katz)  with  slight  de- 
composition. It  dissolves  readily  in  hot  alcohol,  glacial  acetic  acid, 
ether,  and  chloroform,  but  is  practically  insoluble  in  light  petroleum 
ether. 

By  repeated  recrystallization  from  alcohol  or  boiling  with  alcohol, 
the  blue  nitrosite  is  gradually  converted  into  the  white  iso-nitrosite, 
the  melting  point  continually  increasing. 

Humulene  iso-nitrosite,  CisHg^NMOs.  The  oily  mother 
liquors  obtained  in  the  preparation  of  the  blue  nitrosite,  deposited 
a  second,  and  even  a  third  crop  of  crystals.  These,  after,  recrystal- 


is  Journ.  Chem.  Soc.,  67,  p.  781. 
19  Journ.  Chem.  Soc.,  67,  p.  782. 


94 

lization  from  alcohol  were  colorless  and  appear  to  have  the  same 
composition  as  the  blue  compound.  Chapman  considers  this  as  the 
iso-nitrosite  and  the  blue  compound  as  the  true  nitroso  derivative 

This  same  white  compound  is  obtained  by  repeatedly  crystallizing 
the  blue  nitrosite  from  alcohol,  or  simply  by  heating  it  with  alcohol 
for  several  hours.  During  the  recrystallization  the  crystals  become 
paler  and  finally  white,  and  the  melting  point  gradually  rises  from 
about  120°  up  to  166—168°.  It  melts  with  decomposition. 

That  this  behavior  of  the  blue  compound  is  probably  due  to  the 
action  of  light,  as  was  observed  by  Schreiner  and  Kremers  for  the 
corresponding  caryophyllene  compound,  has  already  been  pointed  out 
in  the  general  discussion. 

Humulene  nitrolbenzylamine,  Ci5H24(NO)NHCH 2(^115. 
Chapman20  prepared  this  base  by  heating  humulene  nitrosochloride 
with  an  excess  of  benzylamine  almost  to  the  boiling  point  of  the 
latter,  and  dissolving  the  product  of  the  reaction  in  alcohol.  By 
adding  a  little  water  the  nitrolbenzylamine  crystallizes  out.  It  can 
be  purified  by  recrystallization  from  alcohol. 

This  nitrol  base  crystallizes  in  bundles  of  very  small  needles  radi- 
ating from  a,  center,  which  melt  at  136°  (Chapman)  132 — 133° 
(Fichter  and  Katz). 

Hydrochloride.  By  passing  hydrochloric  acid  gas  into  a 
solution  of  humulene  nitrolbenzylamine  in  dry  ether,  the  hydrochloride 
of  this  base  separates  as  a  white,  granular  precipitate.  It  can  be 
purified  by  several  recrystallizations  from  boiling  water,  and  melts 
at  187 — 189°  with  decomposition. 

Humulene  nitrolpiperidine,  Ci5H24(NO)NC5Hio.  This  com- 
pound is  prepared  by  Chapman21  in  precisely  the  same  manner  as 
that  described  for  the  benzylamine  base.  It  is  purified  by  recrystal- 
lization from  hot  alcohol. 

The  nitrolpiperidine  base  is  but  slightly  soluble  in  cold,  some- 
what more  soluble  in  hot  alcohol.  It  crystallizes  in  the  form  of 
small,  white,  glistening  plates.  Melting  point  153°  (Chapman)  151 
to  152°  (Fichter  and  Katz). 

Hydrochloride.  The  hydrochloride22  is  precipitated  by  passing 
hydrochloric  acid  gas  into  an  ether  solution  of  the  nitrolamine.  It 
is  purified  by  recrystallization  from  boiling  water  or  from  alcohol. 

20  Journ.  Chem.  Soc.,  67,  781. 

21  Journ.  Chem.  Soc.,  67.  p.  62. 

22  Journ.  Chem.  Soc.,  67,  p.  780. 


95 

From  water  it  crystallizes  in  hard  nodular  masses.  No  melting  point 
is  given. 

Platinochloride  (Ci5H24.NO.NC5Hio)2H2PtCl6.  This  com- 
pound is  prepared  23  by  mixing  alcoholic  solutions  of  platinic  chloride 
and  of  the  hydrochloride  of  nitrolpiperidine.  It  crystallizes  from 
alcohol  in  reddish  needles,  melting  at  187—189°  with  decomposition. 

Nitroso-  or  isonitroso  -  humulene,  CisH^NOH.  Fichter 
and  Katz24  obtained  this  compound  by  treating  humulene  nitroso- 
chloride  with  sodium  ethylate.  It  is  a  yellow  viscous  oil,  distilling 
at  185—195°  (13  mm.)  and  has  not  been  obtained  in  a  crystalline 
condition.  By  reduction  a  base  was  obtained,  but  it  could  not  be 
prepared  in  a  pure  condition. 

Chapman  tried  a  similar  reaction  with  humulene  nitrosate  but 
failed  to  get  the  product  of  the  reaction  in  a  pure  form. 

IT.    Ledene. 

Ledene  has  not  been  found  in  nature  but  is  obtained  by  de- 
hydration from  the  so-called  ledurn  camphor,  found  in  the  oil  of 
Ledum  palustre.  Rizza1  in  1887,  recognized  this  so-called  camphor 
as  a  sesquiterpene  hydrate,  and  obtained  from  it  a  sesquiterpene  by 
treatment  with  acetic  acid  anhydride.  Hjelt,2  in  1895,  also  obtained 
the  hydrocarbon  CisH^  and  called  it  ledene. 

Preparation.  Ledene  hydrate  splits  off  water  with  great  ease. 
Ilizza  prepared  the  sesquiterpene  from  ledene  hydrate  by  heating  it 
with  acetic  acid  anhydride  (30  g.  to  5  g.  of  the  hydrate)  in  a  tube 
to  150°  for  5  hours.  The  upper  oily  layer  was  well  washed  with 
alkali  and  dried  with  calcium  chloride. 

Hjelt  prepared  ledene  by  simply  warming  the  hydrate  with  diluted 
sulphuric  acid  (1:1)  on  a  water  bath.  The  upper  oily  layer  was 
distilled  over  with  steam,  separated  and  dried. 

Properties.  Ledene  is  a  colorless  liquid  of  a  very  characteristic 
odor  and  having  the  following  properties: 

Rizza  (1887):   B.  p.  264  (752mm.);  d0°  =  0.9349;  di9°=^0.9237. 

Hjelt  (1895) :  B.  p.  255°. 

The  chemical  study  of  ledene  is  restricted  to  the  statement  that 
bromine  is  absorbed. 


23  Journ.  Chem.  Soc.,  67,  p.  781. 
2*  Ber.,  32,  p.  3184. 

1  Journ.  <1.  russ.  phys.-chem.  Ges.,  1887,  (1»,  p.  319;  Ber..  20,  Kef.,  p.  562. 

2  Ber.,  28,  p.  3087. 


90 

Sesquiterpene  hydrate  yielding  ledene.  Ledene  hyd- 
rate. Ledene  hydrate  separates  from  the  water  of  distillation  and 
also  from  the  oil  of  Ledum  palustre.  It  was  obtained  by  Grassmarm3 
as  early  as  1831  and  was  later  studied  by  Frapp4  (1869),  Ivanow5 
(1876),  Hjelt'and  Collan^  (1882),  Rizza  ?  (1883).  Rizza8  in  1887 
and  Hjelt9  in  1895  recognized  the  compound  as  a  sesquiterpene 
hydrate. 

Preparation.  As  already  mentioned  the  hydrate  separates 
from  the  oil  on  cooling  and  is  also  obtained  from  the  water  of 
distillation.  It  can  be  purified  by  crystallization  from  alcohol, 
benzol,  ether  or  chloroform.  It  crystallizes  in  nice  prismatic  crystals 
from  these  solvents  and  can  also  be  obtained  in  the  form  of  long 
white  needles  by  sublimation. 

Properties.  The  physical  constants  of  ledene  hydrate  are  as 
follows : 

Rizza  (1883):    M.  p.  104—105°. 
Hjelt  and  Collan  (1882):  M.  p.  101°. 

Hjelt  (1895):  M.  p.  104-105°;  b.  p.  282-283°;  [«]j  ==  +7.98° 
in  10  p.  c.  alcoholic  solution. 

As  mentioned  above  ledene  hydrate  is  readily  dehydrated  to  form 
ledene.  Chemically  ledene  hydrate  behaves  like  a  tertiary  alcohol. 
Potassium  permanganate  does  not  act  upon  it.  No  chemical  deri- 
vatives have  been  prepared.  Benzoyl  chloride  appears  to  act  on  the 
hydrate  with  evolution  of  hydrochloric  acid  gas  and  formation  of 
an  oil  having  the  properties  of  ledene.  Phenylcyanate  acts  upon 
it  and  a  small  amount  of  a  substance  melting  at  144 — 145°  was  ob- 
tained by  Hjelt,  which  may  have  been  a  urethane.  Phosphorus 
chloride  acts  on  the  hydrate  in  ligroin  solution  to  form  a  chloride 
which  could  not  be  obtained  in  a  pure  condition.  Heated  with 
quinoline  the  chloride  gave  rise  to  an  oil  having  the  boiling  point  of 
ledene,  namely  255°. 


Buchner,  Repert,  fur  Pharni.,  38,  p.  53. 

Ztsch.  f.  Chem  ,  1869,  p.  350;   Ber.,  8,  p.  542. 

Russ.  Ztsch.  Pharm.,  1876,  p.  577;   Jahrb.  1876. 

Ber.,  15,  p.  2500. 

Journ.  d.  russ.  phys.-chem.  Ges.,  1887,  (1),  p.  319;    Ber.,  20,  Ref.,  p.  562. 

Ber,,  28.  p.  3087. 

Prot.  d.  russ.  phys.-chem.  Ges.,  1883,  p.  362:   Ber.,  16,  Ref.,  p.  2311 


97 


Patchoulene  does  not  occur  in  nature  but  is  prepared  by  dehydrat- 
ing the  socalled  patchouly  camphor,  more  correctly  termed  patchouly 
alcohol  by  Wallach.  Gal1  in  1869  obtained  from  this  alcohol  by 
dehydration  a  hydrocarbon  boiling  at  248—252°,  to  which  he  assigned 
the  formula  CisHae.  Montgolfier 2  in  1877  also  obtained  the  hydro- 
carbon from  patchouly  camphor  and  recognized  its  nature  as  a 
sesquiterpehe,  Ci5H24.  Wallach  and  Tuttle3  further  investigated  the 
sesquiterpene  in  1894,  but  so  far  it  has  not  been  sufficiently  well 
characterized  to  be  designated  as  a  chemical  individual. 

Preparation.  Gal  prepared  the  hydrocarbon  by  treating 
patchouly  alcohol  with  zinc  chloride.  Montgolfier  simply  heated  a 
solution  of  the  alcohol  in  glacial  acetic  acid  to  100°  for  several  hours. 
The  hydrocarbon  separated  in  a  layer,  was  washed  and  purified. 
Wallach  and  Tuttle  prepared  patchoulene  by  heating  the  alcohol 
with  potassium  bisulphate  in  a  paraffin  bath  to  180°  for  one  and 
one-half  hours.  The  separated  hydrocarbon  was  washed  and  purified 
in  the  usual  way. 

Properties.  Patchoulene  has  a  cedar-like  odor  resembling  the 
cedrene  obtained  from  cedarwood.  It  is  slightly  soluble  in  alcohol 
and  glacial  acetic  acid,  soluble  in  all  proportions  in  ether,  benzin  etc.. 
and  has  the  following  physical  constants : 

Gal  (1869):  B.  p.  248-252°. 

Montgolfier  (1877):  B.  p.  252—255°  (743  mm.),  do°  =  0.946, 
di8.5°  =  0.937;  [a]D=  -42°  10'. 

Wallach  (1894):  B.  p.  254-256°;  das0  =  0.939;  nD  =  1.50094. 

i 
The  molecular  refraction  =  64.02 ;  calculated  for  CisH24l=  =64.45. 

According  to  Montgolfier  patchoulene  does  not  combine  with 
hydrochloric  acid.  Wallach  and  Tuttle  report  no  chemical  work. 

Sesquiterpene  hydrate  yielding  patchoulene.  Patch- 
ouly alcohol.  This  alcohol,  formerly  called  patchouly  camphor, 


t  Montgolfier,  C.  r.  84,  p.  88.    Sometimes  called  patchoulin  (Beilstein  III, p.  538). 

1  Compt.  rend.,  68,  p,  306;  Ann.,  150,  p.  374. 

2  Compt-  rend.,  84,  p.  88. 

3  Ann.,  279,  p.  8<>4. 
*  Ann.  271,  p.  299. 


98 

separates  occasionally  from  patchouli  oil  on  long  standing.  Gal  in 
1869  studied  this  substance  and  gave  it  the  formula  CisH^sO.  Mont- 
golfier  in  1877  recognized  the  compound  as  being  isomeric  with  the 
so-called  cubeb  and  cedar  camphor  and  gave  it  the  formula  CioHueO. 
Wallach4  in  1892  proposed  the  name  of  patchouly  alcohol. 

Properties.  Patchouly  alcohol  is  soluble  in  alcohol  and  ether 
and  crystallizes  in  well  developed  hexagonal  prisms  ending  in  six-sided 
pyramids.  It  has  been  found  to  have  the  following  properties; 

Gal  (1869):    M.  p.   54—55°:  b.  p.  296°;  d±.5°  ==  1.051;    [«]„  = 
—95.79°  in  a  19  p.  c.  alcoholic  solution. 

Montgolfier  (1877):  M.  p.  59°;  d  =-•  about  1.0;  [«]D  =  118°, 
somewhat  less  in  alcoholic  solution. 

Wallach  and  Tuttle  (1894):  M.  p.  56°. 

Patchouty  alcohol  decomposes  very  readily  into  water  and  hydro- 
carbon. The  weakest  dehydrating  agents,  such  as  dilute  sulphuric 
or  hydrochloric  acids,  or  acetic  acid  anhydride  in  the  cold  or  simply 
heating  the  compound,  will  readily  split  off  water,  although  this  is 
best  accomplished  by  the  method  described  above  for  the  preparation 
of  patchoulene.  The  behavior  of  patchouli  alcohol  shows  that  the 
hydroxyl  is  in  a  tertiary  position.  According  to  Wallach  and  Tuttle 
the  compounds  produced  by  replacing  the  hydroxyl  by  halogen  are 
exceedingly  unstable  and  split  off  halogen  acid  immediately. 

19.    Rhodiene. 

Gladstone1  obtained  from  oil  of  rhodium2  (rosewood)  a  sesqui- 
terpene  of  the  following  properties: 

B.  p.  249°;   d2o°  =  0.9042;   «D— — 11°;   nc=  1.4911. 

It  had  an  odor  of  sandalwood  and  roses  and  combines  with 
hydrochloric  acid,  but  no  hydrochloride  of  definite  composition  could 

be  obtained.3 

20.    Santalenes. 

History  and  General  Discussion. 

The  hydrocarbons  known  as  a-  and  /3-santalene  have  so  far  been 
found  only  in  sandalwood  oil.  This  oil  has  been  investigated  by  a 
number  of  chemists  during  the  last  twenty  years,  but  the  literature 


1  Journ.  Chera.  Soc.,  17,  p.  1;    Briihl.  Ber.,  21.  p.  148  table. 

2  According    to    Gilcleineister    and    Hoffmann,     Die    Aeth.    Oele,    p.    778,     oil    of 
rhodium  Is  often  a  mixture  of  sandalwood  or  eedarwood   oil    with   rose  oil.     There 
is  no  evidence  that  the  oil  examined  by  Gladstone  was  true  ojl  of  rhodium,  distilled 
from  Convolvulus  scop&rius. 

s  Pharra.  Journ.,  31,  pp.  687,  688, 


99 

on  the  subject  is  quite  contradictory.  As  far  as  the  sesquiterpenes 
contained  in  the  oil  are  concerned,  Guerbet  has  shown  that  there  are 
two,  the  a-  and  ,2-santalene  mentioned  above.  These  he  has  definitely 
characterized  by  the  preparation  of  several  derivatives. 

The  nature  of  the  oxygenated  constituents  is  still  a  matter  for 
discussion,  but  as  some  observers  claim  them  to  be  sesquiterpene 
hydrates,  yielding  sesquiterpenes  by  dehydration,  it  will  be  well  to 
consider  them  in  this  connection  and  to  give  a  brief  exposition  of 
these  conflicting  views. 

Chapoteaut1  in  1882  separated  oil  of  sandalwood  into  two 
fractions,  an  aldehyde  boiling  about  300°  and  having  the  formula 
CisHs-tO,  and  an  alcohol  boiling  about  310°,  of  the  formula  CisH^eO. 
These  two  compounds,  when  treated  with  phosphoric  acid  anhydride, 
yield  hydrocarbons,  Ci5H22  (b.  p.  245°)  and  Ci5H24  (b.  p.  260°) 
respectively.  The  first  of  these  he  considers  as  probably  identical 
with  cedrene,  the  second  with  the  sesquiterpene  of  copaiba  oil. 

Chapman  and  Burgess2  in  1896  isolated  a  fraction  boiling  at 
301 — 306°,  which  they  consider  to  be  an  aldehyde,  santalal,  CisH^O. 
Its  properties  were  as  follows:  cUs!=  0.9793,  d?of—  0.9761;  [a]D  = 

15°  200 

— 14°42/;  nHa  =  1.5051,  nn=t=1.5085.  By  treatment  with  phosphorus 
pentoxide  a  hydrocarbon,  Ci5H22..  of  the  following  properties,  was 
obtained:  d is!  =  0.9359;  b.  p.  140—145°  (25  mm.):  aD  =  +5°  45'. 

15° 

This  hydrocarbon  was  unsaturated,  combined  with  hydrohalogen^ 
oxides  of  nitrogen  and  nitrosyl  chloride,  but  no  definite  compounds 
could  be  obtained.  The  authors  compared  the  hydrocarbon  with 
cedrene  from  cedarwood  oil,  und  conclude  that  it  is  similar  to  but 
not  identical  with  this  hydrocarbon. 

The  chemists  of  Scliimmel  &  Co.3  prepared  santalol,  the  alcohol 
of  sandalwood  oil,  by  saponification  of  the  oil  and  distillation  in  a 
vacuum.  The  crude  santalol  was  further  purified  by  .converting  it 
into  santalyl  phthalic  acid,  from  which  it  was  regenerated  by  sapo- 
nification. The  product  thus  obtained  could  be  separated  by  distil- 
lation in  a  vacuum  into  fractions  which  differed  in  rotatory  power 
from  —7°  20'  to  —32°  36'.  These  chemists,  therefore,  concluded  that 
santalol  was  a  mixture  of  two  alcohols,  of  which  the  lower  boiling 


1  Bull.  Soc.  chim.,  (2)   37,  p.  358. 

2  Troc.  Chem.  Soc.,  189(5,  p.  140;   Chem.  News,  74,  p.  95. 
s  Ber.  v.  S.  &  Co.,  April  1899,  p.  43. 


100 

one  is  inactive  or  perhaps  even  dextrogyrate,  the  higher  boiling  one, 
strongly  laevogyrate.  In  a  later  report4  they  question  the  formula 
CioH260  for  santalol,  since  a  sample  purified  as  stated  above  gave 
on  acetylization  a  result  corresponding  to  103.5  p.  c.  of  santalyl 
acetate.  They  conclude  that  santalol  either  has  a  different  compo- 
sition (possibly  Ci5H220),  or  else  it  is  a  mixture  of  noriisomeric 
alcohols  of  different  composition. 

The  results  of  v.  Soden  and  M  tiller5  published  at  nearly  the  same 
time,  corroborate  the  statement  of  Schimmel  &  Co.,  concerning  san- 
talol being  a  mixture.  These  chemists  also  isolated  a  sesquiterpene 
from  sandalwood  oil,  to  which  they  gave  the  name  santalene. 

Guerbet6  in  1900  isolated  from  sandalwood  oil  two  sesquiterpenes 
which  he  designated  as  «-  and  /3-santalene,  the  latter  being  the  same 
as  the  santalene  of  v.  Soden  and  Miiller.  By  the  preparation  of 
nitrosochlorides  and  nitrol  piperidine  bases,  he  was  able  to  charac- 
terize these  compounds.  The  oxygenated  portion  of  the  oil  he  found 
to  consist  of  an  aldehyde,  santalal,  and  two  sesquiterpene  hydrates. 
a-  and  /?-santalol.  These  santalols,  when  treated  with  phosphoric 
acid  anhydride,  yield  sesquiterpenes,  which  Guerbet  has  called  «-  and 
/?-iso-santalene  respectively. 

In  the  same  year  v.  Soden7  published  somewhat  different  results. 
He  also  succeeded  in  separating  santalol  into  two  alcohols,  of  which 
one  has  the  formula  CisH^O,  and  he  considers  it  likely  that  the 
other  alcohol,  which  has  not  been  prepared  in  a  pure  form,  will  have 
this  same  composition,  whereas  Guerbet  considered  the  alcohols  as 
compounds  CisH^eO.  If  v.  Soden's  formula  Ci5H240  is  correct  for 
«-  and  /9-santalol  then  the  iso-santalenes  obtained  from  them  cannot 
be  sesquiterpenes  as  Guerbet  supposes. 

The  results  obtained  by  these  various  investigators  may  be  briefly 
summarized  as  follows : 

Chapoteaut  (1882):   aldehyde,  Ci5H240;  alcohol,  CisI^eO. 

Chapman  and  Burgess  (1896):  Santalol  (aldehyde)  Ci5H24O. 

Schimmel  &  Co.  (1899—90):  Santalol  consists  of  two  alcohols; 
formula  possibly  Ci;-sH220,  or  else  a  mixture  of  nonisomeric  alcohols 
of  different  composition. 

v.  Soden  and  Miiller  (1899):  Santalene,  Cir,H24;  Santalol  consists 
of  two  alcohols. 


*  Ber.  v.  S.  &  Co.,  April  1900,  p.  47. 

5   I'harm.  Ztg.,  44,  p.  25S. 

s  Compt.  rend.,  130,  pp.  417,  1324;  Bull.  Soc.  chim.,  (3)  23,  pp.  218,  540. 

7  Arch.  (1.  Pharm.,  238,  p.  353. 


101 

Guerbet  (1900) :' a-  and  /?-santalene,  Cir>H24;  santalol  (aldehyde), 
CisH240;  a-  and  p'-santalol,  CisH^eO. 

v.  Soden  (1900) :  Santalol  consists  of  two  alcohols  CisH^O. 

This  summary  clearly  shows  the  contradictory  nature  of  the 
various  reports.  Whether  this  is  due  to  a  varying  composition  of 
the  oil,  or  to  the  impure  compounds  subjected  to  analysis,  must  be 
left  for  future  work  to  decide.  Probably  none  of  the  above  investi- 
gators had  an  absolutely  pure  chemical  unit  under  consideration, 
for  the  separation  was  accomplished  by  repeated  distillation  the  boil- 
ing points  of  the  alcohols  being  quite  close  together. 

a-  and  /5-Santalene. 
Preparation. 

The  santalenes  have  been  prepared  only  by  fractional  distillation 
from  sandalwood  oil.  Guerbet  *  prepared  the  sesquiterpenes  as  follows : 
Oil  of  sandalwood  is  saponified  with  alcoholic  potash,  and  the  pro- 
duct well  washed  with  water  and  dried  with  potassium  carbonate. 
This  saponified  oil  is  then  subjected  to  several  fractionations  under 
diminished  pressure.  The  oil  is  thus  separated  into  groups  of  frac- 
tions, the  first  group  passing  between  110 — 180°  (38  mm.)  and  the 
second  between  180—200°  (38  mm.).  The  first  consists  chiefly  of 
hydrocarbons,  the  second  of  oxygenated  constituents. 

Separation  of  a-  and  /3-santalenes.  The  hydrocarbon 
fraction  from  the  sandalwood  oil  was  then  fractionated  many  times, 
at  first  in  a  vacuum,  and  later  under  atmospheric  pressure,  using  a 
Le  Bel-Henninger  distilling  column.  Proceeding  in  this  manner, 
Guerbet  was  able  to  separate  the  hydrocarbon  fraction  into  two 
distinct  sesquiterpenes,  differing  about  ten  degrees  in  boiling  point, 
and  yielding  different  derivatives.  Guerbet,  as  stated,  distinguished 
between  them  by  calling  the  lower  boiling  hydrocarbon,  «-  and  the 
higher  boiling  hydrocarbon,  /S-santalene. 

This  latter  compound  had  already  been  prepared  by  v.  Soden 
and  Miiller  in  1899  by  repeated  fractionation  of  the  saponified  oil, 
and  called  by  them,  santalene. 

Physical  Properties. 

According  to  Guerbet6  and  also  to  v.  Soden  and  Miiller5  the 
physical  properties  of  the  santalenes  are  as  follows: 


102 

a-Santalene. 

Guerbet  (1900):  B.  p.  252—252.5°;  d0°  =  0.9134;  «D  =  -13.98°. 
/3-Santalene. 

v.  Soden  and  Miiller  (1899):  B.  p.  261-262°;  diB°  =  0.898; 
aD  =  about  —21°. 

Guerbet  (1900):  B.  p.  261-262°;  d0°  =  0.9139;  «p  =    -28.55°. 

According  to  v.  Soden  and  Miiller  the  ^-santalene  is  soluble  in 
about  16  parts  of  90  p.  c.  alcohol  and  readily  soluble  in  chloroform, 
ether,  benzene,  and  petroleum  ether. 

Chemical  Properties  and  Derivatives. 

The  santalenes  combine  with  two  molecules  of  hydrohalogen  or 
bromine,  but  no  crystalline  derivatives  have  been  obtained.  The 
hydrate  and  acetate  are  likewise  liquid  compounds.  Guerbet  succeeded 
in  preparing  nitrosochlorides  of  both  the  «-  and  /2-santalene  and  from 
these  the  nitrolpiperidine  base.  /3-santalene  yielded  two  distinct 
nitrosochlorides,  which  were  separated  by  fractional  crystallization 
from  alcohol.  A  nitrosate  could  not  be  obtained.  According  to 
Guerbet  both  sesquiterpenes  oxidize  readily  in  the  air  and  give 
a  color  reaction  which  is  quite  different  from  that  given  by  cadinene. 
Santalene  when  dissolved  in  glacial  acetic  acid  and  treated  with  a 
drop  or  two  of  sulphuric  acid,  gives  a  currant  red  color,  which  be- 
comes deeper  and  finally  changes  to  brown  after  standing  several 
hours.  Cadinene  under  the  same  conditions  gives  a  fine  green  color, 
changing  to  blue,  and  on  heating  to  red. 

Santalene  dihydrochloride,  Ci5H242HCl.  H.  v.  Soden  and 
Miiller11  mention  the  addition  of  two  molecules  of  hydrochloric  acid 
to  santalene  (/3-santalene,  Guerbet),  but  they  did  not  obtain  it  in 
pure  form.  Guerbet12  reports  more  fully,  but  also  had  only  impure 
liquids  under  consideration,  as  the  dihydrochlorides  resisted  all 
attempts  at  purification.  He  proceeded  as  follows :  Dry  hydrochloric 
acid  gas  was  passed  into  a  well  cooled  solution  of  santalene  in  ether 
up  to  saturation,  and  the  solution  allowed  to  stand  for  a  time. 
The  ether  was  then  evaporated  and  the  oil  kept  for  a  long  time  in 
a  vacuum  over  caustic  potash.  An  analysis  of  this  impure  product 
gave  results  agreeing  quite  well  with  the  formula  Cir>H242HCl.  By 
distillation  in  a  vacuum  the  hydrochloride  decomposes. 

11  Pharm.  Ztg.,  44,  p.  259. 

12  Bull.  Soc.  chim.,  (8)  23,  p.  541. 


103 

The  rotatory  power  of  the  santalenes  has  suffered  an  inversion 
by  the  change  to  the  dihydroehlorides : 

«-Santalene  dihydrochloride,  «»==  +6°. 
/3-Santalene  dihydrochloride,  aw  =  +8°. 

Santalene  nitrosochlorides,  CisH^.NOCl.  H.  v.  Soden  and 
Miiller13  did  not  succeed  in  the  preparation  of  this  derivative. 
Guerbet1*  states  that  the  general  method  of  Wallach  gave  but  an 
insignificant  yield.  He  obtained  a  yield  of  about  50  p.  c.  by  dis- 
solving the  santalene  in  petroleum  ether  and  adding  to  this  a  solu- 
tion of  nitrosyl  chloride  in  the  same  solvent,  keeping  the  mixture  at 
a  low  temperature. 

« -Santalene  nitrosochloride.  a-Santalene  yields  only  one 
nitrosochloride.  It  is  crystalline,  insoluble  in  alcohol,  and  only 
slightly  soluble  in  ordinary  ether,  but  very  soluble  in  petroleum  ether 
and  in  benzol.  From  a  solution  in  the  latter  solvent  it  is  deposited 
in  small,  short  prismatic  crystals,  melting  at  122°  with  decomposi- 
tion. It  yields  a  nitrolpiperidine  base. 

(3-  San  tale  ne  nitroso  chlorides.  /3-Santalene  yields  two  iso- 
meric  nitrosochlorides.  Both  are*  soluble  in  alcohol,  which  fact 
distinguishes  them  from  a-santalene  nitrosochloride.  They  are  also 
more  stable  when  heated  and  can  be  melted  without  decomposition. 

The  two  isomeric  /3-santaIene  nitrosochlorides  are  separated  by 
fractional  crystallization  from  95  p.  c.  alcohol.  The  nitrosochloride 
least  soluble  in  the  alcohol,  crystallizes  in  large  striated  tablets  and 
melts  at  152°;  the  other,  present  in  much  larger  quantity,  crystal- 
lizes in  prismatic  needles,  melting  at  106°.  Both  yield  nitrolpiperi- 
dine bases. 

Santalene  nitrolpiperi dines,  CisEtaCNOJNCsHio.  Guerbet 
obtained  three  distinct  nitrolpiperidine  bases  by  treating  the  three 
nitrosochlorides  with  piperidine. 

a- Base.  This  was  obtained  from  the  «-santalene  nitrosochloride 
by  treating  with  piperidine  in  benzene  solution.  It  is  very  soluble  in 
alcohol,  from  which  it  crystallizes  in  fine  needles  melting  at  108 — 109°. 

/?- Bases.  There  are  two  Abases  obtained  from  the  two  /?-nitroso- 
chlorides  described  above.  Both  are  soluble  in  alcohol  and  melt  at 
101°  and  104—105°  respectively. 


is  Pharm.  Zt#..  44,  p.  i' .">'.». 

i*  Bull.  Soc.  chim.,  (<3)  23,  p,  541, 


104 


Santalene  acetates,  OisH^CsHiOs.  According  to  Guerbet, 
when  a-  and  /3-santalenes  are  heated  to  180—190°  in  sealed  tubes 
with  glacial  acetic  acid,  the  sesquiterpenes  slowly  combine  with  it  to 
form  acetates.  Guerbet  obtained,  however,  a  yield  of  only  2.5  p.  c. 
The  acetates  are  colorless  liquids  of  agreeable  odor. 

a-Acetate  boils  at  164—165°  (14  mm.). 

/?-  Acetate  boils  at  167—168°  (14  mm.). 

Santalene  hydrate,  CisH^sOH.  Guerbet  could  not  prepare 
a  hydrate  of  a-  and  /3-santalene  as  had  been  done  by  v.  Soden  and 
Miiller15  with  santalene  (/?-santalene,  Guerbet).  These  chemists  pre- 
pared a  hydrate  by  a  method  similar  to  that  described  for  caryo- 
'phellene  hydrate  (see  this).  From  the  product  of  the  reaction  these 
chemists  isolated  a  small  amount  of  an  alcohol,  CisH^OH.  It  had 
an  odor  resembling  cedarwood  oil  and  the  following  constants  : 

B.  p.  160—165°  (7  mm.);   di5  =  0.978;   optically  inactive. 

«-  and  /s'-Iso-Santalene. 

Guerbet16  obtained  «-  and  /3-iso-santalene  by  the  dehydration  of 
«-  and  /?-santalol  respectively.  The  compound  corresponding  to  the 
a-santalol  of  Guerbet  (and  possibly  also  /2-santalol)  is,  however,  con- 
sidered as  an  alcohol  of  the  formula  CisH240,  by  v.  Soden.17  Should 
this  be  true,  the  hydrocarbons  obtained  by  dehydration  from  these 
alcohols,  would  have  the  formula  Ci5H22,  and  would,  therefore,  not 
fall  into  the  class  of  the  sesquiterpenes. 

According  to  Guerbet,  phosphoric  acid  anhydride  acts  very  vio- 
lently on  the  santalols,  but  by  cooling  with  ice  water  before  adding 
the  dehydrating  agent,  the  reaction  can  be  moderated.  At  best  the 
yield  of  hydrocarbon  is  small,  amounting  to  about  42  p.  c.  of  the 
crude  hydrocarbon.  This  crude  hydrocarbon  is  purified  by  rectification 
under  reduced  pressure. 

The  iso-santalenes  are  colorless  liquids  of  a  terebinthinate  odor 
and  have  the  following  properties: 

«-Iso-santalene;  b.  p.  255—256°;  aD=+0.20. 
/3-Iso-santalene;  b.  p.  259—260°;  «Dr=-f6.1°. 

Alcohols  yielding  the  iso-santalenes.  Santalol  (Go- 
norol).18  Schimmel  &  Co.19  prepare  santalol  by  heating  East  Indian 

is  Pharm.  Ztg.,  44,  p.  259. 

16  Bull.  Soc.  chim.,  (3)  28,  p.  543. 

17  Arch.  d.  Pharm.,  288.  p.  353. 

is  Trade  name  given  by  Heine  &  Co. 
19  Ber    v.  S.  &  Co.,  April  1899,  p.  43. 


105 

sandalwood  oil  with  an  equal  weight  of  phthalic  acid  anhydride  and 
benzene  for  one  hour  to  80°  on  a  water  bath.  The  acid  esters  formerl  - 
are  combined  with  alkali  and  dissolved  in  much  water.  This  aqueous 
solution  is  then  shaken  three  times  with  ether  to  remove  the  non- 
alcoholic constituents.  The  acid  esters  are  then  again  liberated  by 
treating  with  dilute  sulphuric  acid  and  after  separating  they  are 
saponified  with  alcoholic  potash  and  washed  with  water. 

Guerbet20  saponified  the  oil  and  separated  it  into  two  fractions 
by  several  distillations  under  diminished  pressure,  as  already  described 
under  santalene.  The  higher  boiling  fraction  was  then  treated  in  a 
manner  similar  to  that  employed  by  Schimmel  &  Co. 

H.  v.  Soden21  also  saponified  the  oil  and  then  separated  the 
santalol  from  the  sesquiterpenes  by  repeated  distillation  under  dimi- 
nished pressure. 

Separation  into  a-  and  /?-santalol.  Schimmel  &  Co.,  and 
also  v.  Soden  and  Miiller,  showed  that  santalol  was  a  mixture  of 
alcohols.  Guerbet22  succeeded  in  separating  santalol  into  two  alco- 
hols, CioH2oO,  which  he  considered  as  isomeric,  by  repeated  fraction- 
ation  under  diminished  pressure.  These  alcohols  Guerbet  distinguished 
as  «-  and  /?-santalol,  H.  v.  Soden23  separated  the  oil  into  a  number 
of  fractions  by  repeated  distillation.  In  this  way  he  was  able  to 
effect  a  partial  separation  of  «-  and  ^-santalol.  The  /3-santalol  was 
not  prepared  in  a  purer  condition,  but  the  crude  «-santalol  was 
purified  by  converting  it  into  an  acid  ester  of  phthalic  acid,  much  in 
the  same  manner  as  already  described  for  santalol,  and  then  frac- 
tionating under  diminished  pressure. 

The  physical  properties  of  these  alcohols  are  as  follows:  The 
results  of  Guerbet  and  v.  Soden  only  are  given  as  these  chemists  had 
undoubtedly  purer  products  under  consideration  than  earlier  workers, 
and  also  because  the  alcohols  having  these  specific  properties  were 
used  in  the  preparation  of  the  iso-santolenes  described  above. 

a-Santalol. 

Guerbet:  formula  CinH^O;  b.  p.  162—163°  (13mm.),  300— 

301°  (760mm.);  do°  =  0.9854;   ,/n=-1.20°. 
v.  Soden:  formula  Ci5H240;  b.  p.  155°   (8  mm.),  301—302° 
(752  mm.);  d15°  =  0.977;  «D  ==  +1°  40'  to  2°  4'. 

20  Bull.  Soc.  chim.,  (3)  23,  p.  218. 

21  Arch.  d.  Pharm.,  238,  p.  357. 

22  Bull.  Soc.  chim.,  (3)  23,  p.  23,  pp.  219,  543, 
8'»  1,  c. 


106 

£-Santalol. 

Gourbet:  formula  Ci5H260;  b.  p.  170—171  (14  mm.),  309— 
310  (760  mm.);  do°  =  0.9868;  ffl)=— 56°. 

21.    Sesquiterpene  of  Ageratum  Oil. 

The  oil  distilled  by  van  Romburgh*  from  the  fresh  herb  of  Agera- 
tum  conyzoi'des  has  the  sp.  gr.  1.015  at  27.5°;  «D  =  —  2.75°  and 
boils  at  about  260°.  'The  oil  probably  contains  compounds  belong- 
ing to  the  group  of  sesquiterpenes. 

22.    Sesquiterpene  from  Amyrol. 

H.  v.  Soden  and  Rojahn1  obtained  a  Sesquiterpene  from  amyrol 
by  the  action  of  acid  agents,  but  no  statements  as  to  its  properties 
are  made. 

Amyrol.  This  Sesquiterpene  alcohol  is  obtained  from  West  In- 
dian sandalvvood  oil,  which  is  not  a  true  sandalwood  oil,  but  a 
product  of  Amyris  balsam!  fera,  nat.  ord.  Rutacea?.  Its  similarity  to 
East  Indian  sandalwood  oil  gave  rise  to  the  supposition  that  it  also 
contained  Sesquiterpene  alcohols.  This  suspicion  was  verified  by 
Duliere2  in  1897  who  acetylized  the  oil  and  then  saponified  the  acetic 
esters  formed.  On  the  basis  of  his  results  he  calculates  42  p.  c.  of 
alcohol  as  santalol. 

In  1900  v.  Soden3  isolated  from  the  oil  by  fractional  distillation 
under  diminished  pressure,  an  alcohol  CisH^OH,  which  was  different 
from  santalol,  and  for  which  he  proposed  the  name  of  amyrol.  It 
had  a  specific  gravity  of  0.980—0.982  at  15°  and  a  rotation  of  about 
+  27°;  it  boiled  at  299-301  (748  mm.),  151-152°  (11  mm.). 
Attempts  to  prepare  the  phthalic  acid  ester  failed,  water  bring  split 
off  and  a  Sesquiterpene  generated.  The  acetylization  is  not  quanti- 
tative for  the  same  reasons. 

In  a  second  communication  by  v.  Soden  and  Rojahn4  amyrol  is 
reported  as  consisting  of  two  Sesquiterpene  alcohols.  The  two  alco- 
hols were  separated  by  repeated  fractional  distillation.  The  higher 
boiling  alcohol  has  the  composition  CisHssOH.  It  is  very  viscous 
and  has  a  peculiar  aromatic  odor  and  the  following  properties: 
di5°  =  0.987;  an^  +36°;  b.  p.  299°. 

*  Ber.  v.  8.  &  Co.,  April  1898,  p.  57 

1  Pharm.  Ztg.,  145,  pp.  229,  878. 

2  Bull.  d.  1'academie  roy.  d.  M<?d.  d.  Belgiqne,  (4),  9,  p.  769. 

3  Pharm.  Ztg.,  45,  p.  229. 

*  Pharra.  Ztg.,  45,  p.  878, 


107 

With  dehydrating  agents,  such  as  mineral  acids,  etc.,  it  yields  a 
sesquiterpene.    The  lower  boiling  alcohol  appears  to  have  the  com- 
position CisHasOH  and  to  be  optically  inactive.    Distilled  with  acid  " 
agents,  a  hydrocarbon  results,  which  they  suspect  to  be  1-cadinene. 

23.    Sesquiterpene  of  Angelica  Root  Oil. 

Beilstein  and  Wiegand1  in  1882  obtained  from  the  oxygen  con- 
taining portions  of  angelica  root  oil,  boiling  above  200°,  by  treat- 
ment with  metallic  sodium,  a  fraction  which  boiled  for  the  greater 
part  at  about  250°  and  corresponded  to  the  formula  (CsHg). 

In  1896  Ciamician  and  Silber2  subjected  the  higher  boiling  frac- 
tions of  angelica  root  oil  to  an  examination.  One  of  the  fractions 
on  standing  deposited  crystals  melting  at  74—77°.  The  fraction  was 
distilled  in  a  vaccuum  and  then  saponified  with  alcoholic  potassa. 
The  unsaponified  portion  boiled  between  240  and  270°  and  had  the 
characteristic  odor  of  the  sesquiterpenes.  It  was  not  further  invest- 
igated. 

24.    Sesquiterpene  of  Basilicum  Oil. 

According  to  van  Romburgh3  the  variety  Selasih  besar  of  Oci- 
mum  basilicum,  yields  an  oil  which  contains,  besides  methyl-chavicol, 
eugenol  and  an  olefinic  terpene,  called  ocimene,  a  higher  boiling  com- 
'pound  which  probably  is  a  sesquiterpene.  Further  work  on  this  body 
is  promised. 

25.    Sesquiterpene  of  Calamus  Oil,  Japanese. 

According  to  Schimmel  &  Co.4  the  oil  of  Japanese  calamus  from 
Acorus  spuriosus  boils  between  210—290°.  The  higher  boiling  por- 
tions are  described  as  having  a  "peculiar  sesquiterpene  odor."  Pos- 
sibly this  hydrocarbon  is  identical  with  calamene  from  ordinary 
calamus  oil. 

26.    Sesquiterpene  of  Carline  Thistle  Oil. 

Carline  thistle  yields  about  2  p.  c.  of  a  volatile  oil  which  boils 
for  the  greater  part  between  265—300°.  Its  sp.  gr.  is  1.03  at  18°. 
By  distillation  in  a  vacuum  and  treatment  with  metallic  sodium, 
Semmler5  in  1889  isolated  a  hydrocarbon  belonging  to  the  series 

1  Ber.,  15,  p.  1741. 

2  Ber.,  29.  p.  1811. 

3  Koninklijke  Akademie  von  Westenschappen  te  Amsterdam,  1900,  p.  440 ;   Ber. 
v.   S.  &  Co.,  Apr.  1901,  p.   11. 

*  Ber.,  S.  &  Co.,  April  1SS9.  p.  7. 

••  ('hem.  Ztff.,  p.  1158:  Pharm.  Ztg.,  1888,  p.  G43 ;  Jahresb.  f.  Pharni.,  1889, 
p,  ^57. 


108 


boiling  at  250 — 253°  under  ordinary  pressure  and  having  a 
vapor  density  of  6.78  and  6.82.  Its  specific  gravity  is  very  low  for 
a  sesquiterpene,  being  only  0.8733  at  22.8°.  The  hydrocarbon  which 
is  present  to  the  extent  of  12  p.  c.  in  the  crude  oil,  readily  absorbs 
the  halogens  and  hydrohalogens ;  cone,  nitric  acid  acts  very  violently 
upon  it.  No  crystalline  derivatives  of  any  kind  were  obtained. 

These  data  are  insufficient  to  establish  its  relationship  with 
zingiberene  but,  if  not  identical  with  the  latter,  it  doubtless  belongs 
to  the  same  group  of  sesquiterpenes. 

27.    Sesquiterpene  from  Caryophyllene  Dihydrochloride. 

Schreiner  and  Kremers1  attempted  to  regenerate  caryophyllene 
from  its  dihydrochloride  in  a  manner  similar  to  that  employed  for 
the  regeneration  of  cadinene  from  its  dihydrochloride.  Instead  of 
caryophyllene  they  obtained  an  oil  of  different  properties.  When 
some  of  the  oil,  dissolved  in  petroleum  ether,  was  treated  with  a 
saturated  solution  of  sodium  nitrite  and  glacial  acetic  acid,  the 
petroleum  ether  layer  turned  a  beautiful  blue,  as  it  does  in  the  case 
of  the  nitrosite  of  caryophyllene,  but  no  crystals  could  be  obtained. 
Attempts  to  prepare  other  caryophyllene  derivatives  likewise  failed. 
Its  physical  properties  are  also  different  from  those  of  caryophyllene, 
especially  its  optical  rotation.  Nor  does  it  appear  to  be  identical 
with  clovene,  generated  by  Wallach  from  caryopoyllene  hydrate. 
Wallach  states  that  clovene  is  not  capable  of  uniting  with  nitrosyl 
chloride,  and  it  is,  therefore,  also  incapable  of  uniting  with  the  oxides 
.of  nitrogen.  A  comparison  of  the  sesquiterpene  generated  from 
caryophyllene  dihydrochloride  with  clovene  and  caryophyllene  is  given 
in  the  following  table: 


Caryophyllene. 

Sesquiterpene 
generated  from  cary- 
ophyllene dihydro- 
chloride. 

Clovene. 

SD.  sir... 

0.9039  (20°) 

0.9191  (20°) 

0.930  (18°) 

Index  of  refraction 
Rotation  

1.40976 

-8.96° 

1.49801 
-35.39° 

1.50066 

Whether  this  eesquiterpene  is  an  individual  compound  or  a   mix- 
ture of  caryophyllene  with  another  sesquiterpene  cannot  be  stated. 


I'harm.  Archives. 


109 

The  indications  are,  however,  that  an  inversion  witli    the    possible 

production  of  an  isomer  has  taken  place. 

— -  .  .. 

28.  Sesquiterpenes  of  Cascarilla  Oil. 

In  1899  Thorns1  reports  on  an  oil  of  cascarilla  investigated  by 
Fendler,  who  found  10.5  p.  c.  of  a  sesquiterpene  boiling  at  255—257° 
and  33  p.  c.  of  a  sesquiterpene  boiling  at  260—265°,  as  well  as  11 
p.  c.  of  an  alcohol  Ci5H23(rH  boiling  at  280—290°. 

Fendler2  himself  makes  a  more  detailed  report.  The  lighter  ses- 
quiterpene is  a  light  yellow  oil  of  the  following  properties : 

tl2o°  =  0.911;  [«]„  =  +23.49°;  b.  p.  178-181°  (100  mm.), 
255— 257°  (760  mm.). 

Analysis  shows  the  compound  to  contain  some  oxygen,  but 
attempts  to  remove  this  failed.  Attempts  to  prepare  a  hydrochloride, 
a  bromide,  and  a  nitrosite  likewise  failed. 

The  heavier  sesquiterpene  is  a  light  yellow  oil  and  is  the  principal 
constituent  of  the  oil.  It  has  the  following  properties: 

B.  p.  185—190°  (100  mm.),  260—265   (760  mm.);  d20  =  0.924; 

[«]D=:     +7.36°. 

Analysis  revealed  the  presence  of  oxygenated  constituents  also  in 
this  fraction.  A  molecular  weight  determination  by  the  freezing 
point  method,  gave  195;  calc.  for.  Ci5Ho4  =  204. 

Concerning  the  sesquiterpenes  Fendler  remarks:  "Diese  vollig  zu 
reinigen  und  zu  charakterisieren  resp.  zu  identiflzieren,  ist  nach  dem 
heutigen  Stande  der  Kenntniss  der  Terpene  noch  unmoglich.  Nach 
ihren  Eigenschaften,  welche  von  denen  der  bekannteren  Sesquiterpene 
abweichen,  ist  anzunehmen,  dass  sie  sich  spater  vielleicht  als  neue, 
dem  Cascarillol  eigentiimliche  Korper  erweisen  werden;  moglicherweise 
sind  sie  auch  mit  einem  oder  dem  anderen  der  zahllosen,  teilsbenann- 
ten,  teils  unbenannten,  aber  noch  wenig  charakterisierten  Sesquiter- 
pene identisch.'' 

29.  Sesquiterpene  of  Celery  Seed  Oil. 

In  1897  Ciamician  and  Silber3  examined  the  distillation  residue 
and  the  last  runnings  obtained  in  the  preparation  of  celery  seed  oil. 
The  ethereal  solution  of  the  oil  was  treated  first  with  cold  and  then 
with  hot  alkali,  which  separated  phenols  and  acids.  The  insoluble 

1  Apoth.  Zt£.,  14,  p.  562. 

2  Arch.  d.  Pharm..  238,  688. 

3  Ber.,  10,  p.  496. 


110 

oil  was  found  to  amount  to  about  25  p.  c.  in  the  case  of  the  distil- 
lation residue  and  80  p.  c.  in  the  case  of  the  last  runnings.  It  boils 
for  the  greater  part  between  262  and  209°.  A  test  for  phenol  esters 
gave  a  negative  result  and  an  analysis  gave  results  that  agreed  with 
the  formula  CisH24.  No  solid  hydrochloride  could  be  obtained  by 
treating  with  gaseous  hydrochloric  acid  in  ether  solution.  The  ses- 
quiterpene  was  not  further  investigated. 

29.    Sesquiterpenes  of  Citronella  Oil. 

A  very  exhaustive  investigation  of  citronella  oil  was  made  by  the 
chemists  of  Schimmel  &  Co. 1  in  1899  by  fractionating  100  kilos  of 
oil  by  steam  distillation.  The  17th  fraction  (5  kilos  of  oil)  consisted 
mainly  of  methyl  eugenol  mid  sesquiterpene,  nnd  a  small  amount  of 
geraniol.  The  latter  was  removed  by  fractional  distillation  up  to 
146°  under  18  mm.  pressure.  The  residue  was  than  shaken  out  with 
60  p.  c.  alcohol.  Methyl  eugenol  is  soluble  in  10  parts  of  60  p.  c. 
alcohol,  whereas  the  sesquiterpene  is  but  sparingly  soluble  in  this 
mixture.  This  treatment  was  repeated  eight  times  with  70  p.  c. 
alcohol  and  the  residue  subjected  to  distillation  under  diminished 
pressure.  In  this  way  a  fraction  of  nearly  constant  boiling  point 
was  obtained,  which  had  the  following  properties: 

13.  p.  157°  (15  mm.);  di5°=  0.8643;  aD=  +  1°28';  nD  =  1.5184. 

Under  ordinary  pressure  the  compound  boils  between  270—280° 
with  much  decomposition.  An  elementary  analysis  showed  that  some 
ox3^gen  was  still  present,  but  its  properties  clearly  showed  the  coin- 
pound  to  be  a  sesquiterpene. 

This  sesquiterpene  has  the  lowest  specific  gravity  known  of  any 
member  of  this  class  of  hydrocarbons.  A  calculation,  based  on  the 
index  of  refraction,  as  to  the  number  of  double  bonds  present,  indi- 
cates four  double  bonds.  The  compound  appears,  therefore,  to  be  an 
olefinic  sesquiterpene.  The  hydrocarbon  corresponds  in  its  properties 
to  this  supposition.  It  resinifies  on  standing  for  only  a  day,  halogens 
and  hydrohalogeris  produce  immediate  decomposition  even  in  a 
freezing  mixture:  dilute  permanganate  solution  yields  only  carbonic 
acid,  oxalic  acid  and  a  gly  col-like  body,  soluble  in  water.  The 
hyd  ration  with  acetic  and  sulphuric  acids  (0.1  p.  c.  of  the  latter) 
was  very  incomplete,  the  product  of  the  reaction  showing  a  saponin'-. 
cation  number  of  only  43.6. 

i  Ber.  v.  S.  &  Co.,  Oct.  1899,  p.  12. 


Ill 

Although  no  characteristic  derivatives  of  this  sesquiterpene  could 
be  prepared,  it  is  nevertheless  quite  certain  that  it  is  different  frow 
any  of  the  known  members  of  this  group  in  its  physical  properties. 

The  18th  fraction  (also  5  kilos)  obtained  in  the  fractionation 
of  the  oil  by  steam  distillation  was  treated  in  the  same  way  with 
70  p.  c.  alcohol  and  the  washed  product  distilled  under  diminished 
pressure.  A  second  sesquiterpene  leaving  the  following  properties 
was  thus  obtained: 

B.  p.  272—275°  (700  mm.),  170—172°  (16  mm.);  di5°  =  0.712; 
a»=  +5°  50'. 

On  account  of  the  slight  difference  in  boiling  point  (about  8°)  it 
was  not  possible  to  completely  free  the  heavier  sesquiterpene  from 
the  lighter  compound,  and  the  above  specific  gravity  is,  therefore,  a 
little  low.  No  chemical  work  on  this  heavier  sesquiterpene  is  reported, 
arid  its  identity  with  any  of  the  known  sesquiterpenes  cannot  be 
established  by  means  of  the  data  at  hand. 

30.    Sesquiterpene  of  Copaiba  Balsam  Oil,  African. 

Umney1  has  examined  the  oil  distilled  from  the  so-called  African 
copaiba  balsam.  The  sp.  gr.  of  the  oil  is  0.918  and  it  boils  between 
260—273°.  Its  rotation  in  a  200  mm.  tube  is  +20° 42'.  No  crystal- 
line hydrochloride  could  be  obtained  by  passing  dry  hydrochloric 
acid  gas  into  the  oil,  as  has  been  stated  to  be  the  case  by  Soubeiran 
and  Capitaine2  with  Maracaibo  oil.  Under  similar  treatment  Umney 
has,  however,  also  failed  to  get  crystals  of  a  hydrochloride  from  the 
Maracaibo  variety,  which  result  agrees  in  this  respect  with  the  ex- 
periments of  Brix.3 

The  fraction  boiling  at  264°  was  subjected  to  the  hydration 
method  used  by  Wallach  for  identifying  the  sesquiterpene  of  ordinary 
capaiba  balsam  oil  with  caryophyllene.4  Umney  was  unable  to  get 
a  crystalline  hydrate  from  the  African  variety,  although  fraction 
260°  of  a  South  American  copaiba  oil  yielded  a  small  amount  of  a 
crystalline  hydrate,  identical  with  caryophyllene  hydrate. 

The  failure  to  get  a  crystalline  hydrate,  also  the  rotatory  power 
of  the  oil,  seem  to  indicate  the  absence  rather  than  the  presence  of 
caryophyllene  The  fact  that  this  sesquiterpene  has  been  identified 
in  the  American  varieties,  makes  it  highly  desirable  that  this  oil  be 
subjected  to  the  more  modern  tests.  It  is  not  improbable  that  we 
have  here  a  dextrogyrate  caryophyllene, 

1  Pharm.  Journ.,  (3),  22,  p.  450;   24,  p.  215. 

2  Journ,  Pharm.,  26,  p.  70. 

3  Monatshefte,  2,  p.  507. 

*  8ee  caryophyllune  hydrate. 


112 

31.    Sesquiterpene  of  Cubeb  Oil. 

According  to  Oglialoro1  and  also  Schmidt,2  oil  of  cubebs  contains, 
besides  cadinene,  a  sesquiterpene  of  lower  boiling  point  (262—263°) 
and  lower  rotatory  power,  which  does  not  combine  with  hydrochloric 
acid.  For  discussion  see  cadinene  in  cubeb  oil. 

32.    Sesquiterpene  of  Cypress  Oil. 

According  to  Schimmel  &  Co.3  the  oil  from  the  leaves  and  twigs 
contains  pinene,  and  "probably  sylvestrene  and  a  sesquiterpene." 
No  data  whatever  are  given. 

Cypress  camphor.  From  the  last  running  of  the  oil  distilled 
from  the  leaves  and  young  branches  of  Cnpressns  semper  virens  a 
crystalline  substance  occasionally  separates.4  This  "cypress  cam- 
phor" is  probably  a  sesquiterpene  hydrate,  as  it  resembles  cedar 
camphor  or  cedrol,  from  which  it  differs,  however,  by  being  optically 
inactive.  It  may  possibly  be  the  optically  inactive  modification  of 
cedrol.  From  alcohol  the  compound  crystallizes  in  fine  needles,  from 
petroleum  ether  in  compact  crystalline  masses. 

33.    Sesquiterpene  of  Erechthites  Oil. 

Beilstein  and  Wiegand5  found  fraction  240—310°  of  erechthites 
oil,  after  distillation  from  sodium,  to  correspond  to  the  composition 
CsH8.  The  high  boiling  point  would  seem  to  indicate  a  sesquiterpene. 

Power6  found  the  oil  to  give  Wallach's  color  reaction  for  cadinene. 

34.    Sesquiterpene  of  Garlic  Oil. 

Beckett  and  Wright7  found  in  garlic  oil  a  sesquiterpene,  CisH24> 
boiling  at  253.9°  but  Semmler8  did  not  find  this  compound  in  the 
crude  oil  examined  bv  him. 


1  Ber.,  8,  p.  1357. 

2  Arch.  d.  Pharm.,  191,  p.  22. 

3  Ber.  v.  S.  &  Co.,  Oct.  1894,  p.   71. 
*  G.-H.-K.,  The  volatile  oils,  p.  269. 

5  Ber.,  15.  p.  2852. 

6  Pharm.  Rundschau,  5,  p.  202. 

7  Jahresb,  f.  Chein.,  1876,  p.  898. 
s  Arch,  cl.  Pharm.,  280,  p,  441. 


113 

35.    Sesquiterpene  of  Hemlock  Needle  Oil. 

Bertram  and  Wnlbaum1  report  the  presence  of  a  sesquiterpene  m 
oil  of  hemlock,  but  do  not  identify  it. 

Schimmel  &  Co.2  in  1893  mention  cadinene  as  a  constituent  of 
this  oil,  without,  however,  giving  any  proof  or  reference.  The  same 
is  done  by  Heusler. 3  Gildemeister  &  Hoffmann1  still  mention  the 
sesqniterpene  as  undetermined. 

36.    Sesquiterpene  of  Hemp  Oil. 

Personne5  in  1857  isolated  two  hydrocarbons  from  the  oil  of 
hemp.  These  had  the  formulas  Ci2Hi4  (?)  and  CisH^o-  The  latter 
hydrocarbon  he  called  canntibene.  The  work  of  Valenta  and  also  of 
Vignola  show  cannabene  to  have  been  an  impure  sesquiterpene. 

Valenta6  in  1880  investigated  an  oil  distilled  from  Italian  hemp. 
The  oil  consisted  principally  of  a  sesquiterpene  which  had  the  follow- 
ing properties: 

B.  p.  25G— 258°;  do°=  0.9289;   [«]D= —10.81°. 

With  hydrochloric  acid  it  formed  a  solid  derivative.7  The  oil 
from  the  male  infloresecence  of  Cnnnabis  gigfinten  is  said  to  contain 
the  same  sesquiterpene. 

The  oil  of  hemp  distilled  by  Vignolo 8  in  1895  boiled  between  248 
and  2(58°.  By  repeated  treatment  with  sodium,  he  obtained  an  oil 
boiling  at  25G°.  Its  sp.  gr.  was  0.897  at  15.3°  and  showed  a  slight 
rotation  to  the  left  in  a  chloroform  solution.  The  compound  was 
identified  as  CisHoi  by  analysis  and  vapor  densitj.  With  bromine 
it  yields  a  solid  compound,  but  evidently  undergoes  decomposition 
as  hydrobrornic  acid  is  given  off.  With  hydrochloric  acid  it  yielded 
no  solid  hydrochloride. 

Wood,    Spivey  and  Easterfield9    in  1896  examined  the  resin   of 
Indian  hemp.    From   the  oil  they  separated  a  sesquiterpene,   which 
after  treatment  with  sodium  had  the  following  properties: 
B.  p.  258—259°;   di8°  =  0.898;    [«]»=  —  8.6°. 


1  Arch.  (1.   Pharm.,  231,  p.  295. 

2  Ber.  v.  S.  &  Co.,  Oct.  1803.  Snnpl.  p.  21. 

3  Die  Terpene,  p.  168. 

*  G.-H.-K.,  The  volatile  oils,  p.  264. 
s  Journ.  de  Pharm.,  31,  p.  48. 

6  Gaxz.  chini.,  10,  p.  479;  11,  p.  191;  Ber.  13,  p.  2431;    14,  p.  1717. 

7  G.-H.-K.,  The  volatile  oils,  p.  338. 

*  (Jazz,  chim.,  25,  I,  p.  110;    Ber.,  27,  Ref.  p.  406;    Ber.  v.  S.  &  Co.,  Oct.  1895, 

'•>  Journ.  Chem.  Soc.,  69,  p.  539. 


114 


This  sesquiterpene  absorbed  hydrochloric  acid  and  bromine  but 
no  crystalline  derivatives  were  obtained. 

The  properties  of  the  sesquiterpene  of  hemp  oil  agree  best  with 
those  of  impure  caryophyllene. 

37.    Sesquiterpene  of  Kampferia  Galanga  Oil. 

;  Van  Romburgh  obtained  from  the  oil  of  Kampferia  galanga  a 
bluish  green  fraction  boiling  at  150°  in  a  vacuum  which  probably 
consists  of  a  sesquiterpene.1 

38.    Sesquiterpene  of  Kesso  Root  Oil. 

Bertram  and  Gildemeister2  obtained  from  oil  of  kesso  root  a 
fraction  which  boiled  between  260  and  280°.  It  is  described  as  a 
colorless  liquid  having  a  decided  sesquiterpene  odor.  Attempts  to 
prepare  a  hydrochloride  failed.  The  highest  boiling  portions  consisted 
of  a  blue  oil. 

39.    Sesquiterpene  of  Laurel  Berry  Oil. 

Bias3  isolated  from  the  oil  of  laurel  berries  by  treatment  with 
solution  of  caustic  potassa  a  hydrocarbon  which,  after  distillation 
from  sodium  in  an  atmosphere  of  hydrogen,  had  the  following  pro- 
perties : 

B.  p.  250°;  di5°  =  0.925;  «D  =  -7.23°. 

Analysis  agreed  with  the  formula  Ci5Ho4.  Bias  points  out  that  the 
rotatory  power  agrees  best  with  that  of  the  hydrocarbon  from  oil  of 
rhodium,  which  Gladstone  determined  as  — 11°. 

The  physical  constants  of  this  hydrocarbon  appear  to  agree  best 
with  those  of  caryophyllene  as  shown  by  the  following  tabulation  of 
constants : 


B.  p. 

Sp.gr- 

'.  D 

Caryophyllene 

136—137° 

0  9030 

—8  09° 

(Schreiner  &  Kremers) 
Sesquiterpene 

(20  mm.) 
250° 

(20°) 
0  925 

—7.23° 

Caryophyllene 

258—200° 

0.9085 

active 

(Wallach) 

The  question  might  readily  be  decided  by  means  of  the  nitrosite 
reaction  for  this  hydrocarbon,  if  some  of  the  oil  could  be  obtained. 


1  Ber.  v.  S,  &  Co.,  Oct.  1900,  p.  88. 

2  Arch.  d.  Pharm.,  228,  p.  48(5. 
a  Ann.,  134,  p.  1. 


115 

4-O.    Sesquiterpene  of  Lavender  Oil. 

StMnmler  &  Tiemann  l  obtained  a  small  amount  of  a  sesquiterpene 
boiling  at  130°  under  15  mm.  pressure  from  English  lavender  oft". 
No  other  properties  are  given. 

41.    Sesquiterpene  of  Lemon  Oil. 

According  to  Oliver!2  the  high  boiling  fractions  of  lemon  oil  con- 
tain a  sesqniterpene,  having  the  following  properties: 

B.  p.  240-242°;  d0°  =  0.9847. 
The  tetrabromide  and  dihydrochloride  of  this  body  are  liquids. 

42.    Sesquiterpene  of  Linaloe  Oil. 

Barbier  and  Bouveault3  obtained  from  the  saponified  Mexican 
linaloe  oil,  after  repeated  distillation  under  a  pressure  of  10  mm.  a 
fraction  boiling  between  130  and  140°.  By  treatment  with  sodium 
and  rectification  in  a  vacuum  they  isolated  a  hydrocarbon  boiling 
at  135—136°  (lOmrn.)  and  corresponding  to  the  formula  CisH24  as 
was  shown  by  analysis  and  molecular  weight  determination.  The 
sesquiterpene  absorbs  four  atoms  of  bromine  and  contains,  therefore, 
two  double  bonds. 

The  quantity  of  hydrocarbon  found  in  the  oil  is  about  3  p.  c. 
although  the  authors  state  that  the  amount  is  variable  as  another 
sample  from  an  equally  authentic  source,  contained  very  little  of 
this  hydrocarbon.  The  almost  total  absence  of  physical  constants 
and  chemical  work  is  to  be  regretted. 

43.    Sesquiterpene  of  Long  Pepper  Oil. 

The  oil  of  long  pepper  was  distilled  by  Schimmel  &Co.4  in  1890. 
It  is  described  as  having  a  mild  taste  and  an  odor  reminding  of 
ginger.  It  boils  between  250—300°  and  has  a  specific  gravity  of 
0.8()1  at  15°. 

The  high  boiling  point  and  low  specific  gravity  would  seem  to 
indicate  a  hydrocarbon  of  the  sesquiterpene  series.  The  data  given 
are  insufficient  for  making  a  comparison  with  the  properties  of  zingi- 
berene,  but  it  doubtless  belongs  to  the  same  class  of  the  sesquiter- 
penes  as  the  latter. 

1  Ber.,  25,  p.  1187. 

2  (Jazz,  chim.,  21.  p.  318;    Ber.,  24,   Ref,  p.  (524. 
a  Compt.  rend.,  121,  p.  168. 

*  Ber.  v.  St  &  Co.,  1890,  p.  48. 


116 

4-4-.     Sesquiterpene  of  Minjak-Lagam   Balsam   Oil. 

Minjak-Lagam  balsam  is  closely  allied  to  gurjun  balsam  and  it 
is  not  improbable  that  the  sesquiterpene  from  this  oil  is  identical 
with  the  sesquiterpene  from  gurjun  balsam  oil  (see  Gurjunene). 

Haussner1  in  1883  examined  the  volatile  oil  distilled  from  the 
balsam  with  water  vapor.  The  oil  was  separated,  dried  and  distilled 
in  an  atmosphere  of  carbon  dioxide.  It  had  the  following  properties: 
B.  p.  249-251°;  di5°  =  0.923;  an=  -9.9°. 

The  oil  corresponded  to  the  composition  CioHo4,  although  Hauss- 
ner  gives  the  formula  C2oH32,  based  on  a  vapor  density  determination 
by  Hoffmann's  method,  which,  no  doubt,  gives  too  high  a  result  at 
the  temperature  of  boiling  diphenylene,  viz.  290°.  Exposed  to  air  it 
readily  resinifies. 

Trihydrochloride.  Haussner  succeeded  in  preparing  a  trihydro- 
chloride  of  this  sesquiterpene  by  passing  dry  hydrochloric  acid  gas 
directly  into  the  oil  contained  in  U-tubes  kept  cold  by  a  freezing 
mixture.  The  oil  became  dark  violet  and  very  viscous.  After  standing 
for  some  time  in  the  freezing  mixture,  the  heavy  oil  was  found  to  be 
interspersed  with  crystals.  These  were  separated  by  pressing  on  filter 
paper.  The  oil  absorbed  by  the  paper  was  taken  up  with  alcohol, 
and  after  evaporating  the  solvent  it  was  again  treated  with  hydro- 
chloric acid  gas.  A  second  crop  of  crystals  was  thus  obtained.  The 
crystals  were  purified  by  several  crystallizations  from  alcohol.  The 
analysis  agreed  with  the  formula  Ci5H24.3HCl  or  C2oHa24HCl  as 
Haussner  considers  it. 

The  trihydrochloride  is  soluble  in  alcohol,  ether,  benzol,  and  car- 
bon disulphide.  From  cold  alcohol  it  separates  in  long  (3  cm.) 
white  needles,  melting  at  114°.  From  hot  alcohol  it  separates  in 
felt-like  crystals. 

The  formation  of  this  trihydrochloride  is  rather  surprising,  as  it 
would  indicate  the  presence  of  three  double  bonds  in  the  sesquiterpene. 
For  this,  its  specific  gravity  is,  however,  rather  high.  It  is  to  be 
regretted  that  the  index  of  refraction  was  not  determined  so  that 
the  number  of  double  bonds  might  have  been  calculated  from  this 
physical  constant. 

Beyond  the  preparation  of  the  trihydrochloride  Haussner  obtained 
no  positive  results,  although  he  tried  the  action  of  the  halogens  on 
the  oil. 

i  Arch.  d.  Pharm.,  221,  p.  245. 


117 

4-5.    Sesquiterpene  of  Peppermint  Oil,  English. 

Fiiickiger  and  Power1  separated  from  dementholized  Mitcham  oil 
of  peppermint,  a  fraction  which  after  repeated  rectification  over 
metallic  sodium  had  the  following  properties: 

B.  p.  255-260°;   d2iQ  =  0.912;   «„=  +9°  2'. 

Analysis  agreed  fairly  well  with  the  formula  Ci5Hs4.  Although  the 
oil  was  dextrogyrate  it  is  possible  that  it  was  identical  with  the 
cadinene  found  in  the  American  oil  by  Schimmel  <fc  Co.2 

46.    Sesquiterpene  of  Peppermint  Oil,  Japanese. 

Beckett  and  Wright3  examined  Japanese  oil  of  peppermint  and, 
after  separating  the  menthol,  they  obtained  a  fraction  boiling  at 
245—255°.  This  they  supposed  to  be  a  compound  CgoHsoO  formed  by 
splitting  off  two  molecules  of  water  from  three  molecules  of  the  com- 
pound CioHisO  (menthone?) 


It  is  more  probable  that  the  fraction  consisted  of  a  Sesquiterpene 
(found  in  both  English  and  American  oils)  mixed  with  an  oxygenated 
constituent. 

4-7.    Sesquiterpene  of  Pimenta  Oil. 

In  1864,   Oeser4  investigated  pimenta  oil.    He  dissolved  the  oil 
in   caustic   p  )t:ish    aid    then    treated    it    with    water.    On    heating 
slightly,  an  indifferent  oily  layer  separated.    This  oil,  after  having 
been  dried  and  rectified,  had  the  following  properties  : 
B.  p.  255°;   d8°  =  0.98;   [«]j  =  —  0.49°. 

Analysis  showed  it  to  have  the  formula  (CsH^x  and  on  account 
of  its  high  boiling  point  Oeser  gave  it  the  formula  Cir>H24. 
Oeser  further  thinks  that  it  is  identical  with  the  hydrocarbon  found 
by  Williams3  and  earlier  by  Bruning0  and  by  Ettling7  in  oil  of 
cloves.  This,  however,  appears  not  to  be  the  case,  as  the  specific 
gravity  of  the  hydrocarbon  from  cloves,  now  known  as  caryophyl- 
lene,  is  much  less  than  that  of  the  hydrocarbon  from  pimenta  oil. 
A  more  thorough  investigation  of  this  hydrocarbon  would  doubtless 
prove  interesting. 

i   Pharm.  Journ.,  (2).  11,  p.  22;  Arch.  <1.  IMiarm.,  21S,  p.  222. 

a  Ber.  v.  S.  &  Co..  Apr.  1804.  p.  42. 

3  Journ.  Chem.  Soc..  1876,  I,  p.  3. 

*   Ann.,  181.  p.  277. 

s    Ann.,  107,  p.  242. 

e   Ann.,  104.  p.  202. 

7   Am,.,  9,  p.  68. 


118 

48.    Sesquiterpene  of  Poplar  Bud  Oil. 

Fichter  and  Katz1  in  1899  found  the  sesquiterpene  fraction  of 
poplar  bud  oil  to  consist  chiefly  of  humulene,  but  as  the  yield  of  huinu- 
lene  derivatives  was  smaller  than  obtained  from  the  sesquiterpene  of 
hop  oil,  and  also  because  their  fraction  was  optically  active,  whereas 
the  humulene  of  Chapman'-2  is  inactive,  they  conclude  that  another 
sesquiterpene  accompanies  the  humulene  in  oil  of  poplar  buds.  See 
under  humulene. 

49.    Sesquiterpene  of  Sage  Oil,  English. 

Sugiura  and  Muir3  in  1878  report  on  the  examination  of  a  small 
sample  of  "absolutely  pure  sage  oil"  (English).  It  consisted  for  the 
most  part  of  a  sesquiterpene  having  the  following  properties  : 

B.  p.  264-270°;  d0°  =  0.9198,  d24°  =  0.9072;  au=+3°U'. 

It  had  a  dark  emerald  green  color  and  did  not  form  a  stable 
hydrochloride. 

In  1880  Muir4  confirms  his  previous  work  and  states  that  large 
quantities  of  cedrene  are  present  in  English  sage  oil  distilled  from 
the  leaves.  This  time  he  gives  the  boiling  point  as  260°. 

Although  Muir  calls  the  sesquiterpene  cedrene,  it  is  quite  different 
in  its  properties  from  the  cedrene  obtained  from  cedar  wood  oil.  There 
can  be  but  little  doubt  that  Muir  used  the  name  cedrene  in  the  sense 
suggested  by  Beckett  and  Wright5  in  1876,  who  applied  the  designa- 
tion "cedrenes"  to  all  hydrocarbons  of  the  formula 


5O.    Sesquiterpene    from    Santonin    and    Santonin 
Derivatives. 

Cannizzaro  andAmato0  in  1874  found  that  when  santonic  acid, 
is  treated  with  hydriodic  acid,  there  results  a  hydrocarbon, 
and  an  iodide  CisIIsst.  This  iodide  boils  at  143—145°  under 
5  mm.  pressure.  Distilled  at  ordinary  pressure,  it  decomposes  largely 
into  hydriodic  acid  and  a  sesquiterpene,  Ci5H24. 

According  to  Andreocci7  a  liquid  hydrocarbon  of  the  formula 
Ci5H24  (or  Ci4H22)  boiling  at  247°  results  besides  santonic  acid, 
when  santonin,  CisHisOg,  is  reduced  by  heating  with  stannous 
chloride  and  tin  in  hydrochloric  acid  solution. 

1  Rer,,  32,  p.  3188. 

2  Journ.  Chem.  Sor.,  67,  pp.  54,   780. 

3  Journ.  Chem.  Soc.,  83,  p.  297;    Pharm.  Journ.,  37,  p.  '.(94. 
*  Journ.  Chem.  Soc.,  37,  p.  678. 

=  Journ.  Chem.  Soc.,  (3),  1,  p.  6. 

6  Ber.,  7,  p.  1104. 

7  Ber.,  26,  Ref.  p.  599. 


119 

51.    Sesquiterpene  of  Spike  Oil. 

Bouchardat1  states  that  the  fractions  of  spike  oil  boiling  higher 
than  160°  approach  more  arid  more  the  composition  CisH24  and  he, 
therefore,  concludes  that  the  oil  of  spike  contains  a  hydrocarbon  of 
this  formula. 

52.    Sesquiterpene   (?)  of  Spiraea  Oil. 

Ettling2  obtained  a  small  amount  of  a  hydrocarbon  (OsHs)*  from 
the  oil,  which  was  either  a  terpene  or  a  sesquiterpene. 

53.    Sesquiterpene  of  Valerian  Oil. 

By  repeated  fractionation  under  diminished  pressure,  Oliviero3 
was  able  to  isolate  a  sesquiterpene  and  a  sesquiterpene  hydrate.  The 
fraction  distilling-  between  160  and  165°  under  a  pressure  of  50  mm. 
agreed  fairly  well  with  the  formula  ((V>Hs)x.  It  was  laevorotatory 
—9.2°. 

The  fraction  distilling  between  190  and  195°,  under  the  same 
pressure  (50  mm.)  agreed  fairly  well  with  the  formula  CisH^HaO. 
It  was  dextrorotatory  -f-2.5°  and  had  the  nature  of  an  alcohol  as 
was  shown  by  the  formation  of  a  benzoic  ester  and  a  hydrochloric 
acid  ester. 

In  rotatory  power  this  sesquiterpene  agrees  best  with  that  of 
caryophyllene,  but  in  the  absence  of  other  constants  no  comparison 
can  be  made. 

54.    Sesquiterpene  of  Wild  Thyme  Oil. 

The  higher  boiling  fractions  of  wild  thyme  oil  contain,  besides 
phenols,  hydrocarbons,  presumably  sesquiterpenes,4  but  there  is 
nothing  to  warrant  this  assumption  other  than  the  high  boiling 
point. 

55.    Synthetic  Sesquiterpenes. 

1  —  Methyl  —  4— iso-propyl  — 2—  iso-amyl  benzene. 
(CH3)2.CH.CH2CH2.C6H3(CH3).CH(CH3)2. 

Claus5  has  prepared  a  synthetic  hydrocarbon  of  the  composition 
CisH24,  by  reducing  isobutyl  —  p  —  iso-amyl  ketone  with  iodine  and 
phosphorus  to  1  —  methyl — 4 — isopropyl  —  2  —  iso-amyl  benzene.  It 


1  Compt.  rend.,  117,  p.  55. 

2  Ann.,  35,   p.  243. 

3  Bull.  Soc.  chim.,  11,  (3),   p.  1)24. 

*   G.-H.-K.,  The  volatile  OJ!H,  p.  f>29. 

B   .lourn.  r.  prakt,  Cheni.,  (2),  40,  p.  474;   Chem.  Central!)!.,  1893,  1,  p.  210. 


120 

is  a  colorless,  limpid  oil,  of  faint  valerian-like  odor,  boiling-  at  245° 
and  having  a  specific  gravity  of  0.89  at  17°. 

4  — Octjrl  —  1— methyl  benzene,  C6H4(CH8)C8Hi7. 

Lipinski1  in  1898  prepared  this  synthetic  sesquiterpene  according 
to  Fittig's  reaction.  17  gr.  of  p-bromtoluene,  24  gr.  of  octyl-iodide, 
7  gr.  of  sodium,  and  two  to  three  times  the  volume  of  dry  ether, 
were  used.  The  reaction  took  place  after  a  short  time.  In  order  to 
increase  the  yield,  the  mixture  was  slightly  warmed  toward  the  end 
of  the  reaction,  the  ether  then  distilled  off  and  the  product  of  the 
reaction  fractionated. 

This  synthetic  sesquiterpene  is  a  colorless  oil,  boiling  between 
281—283°  and  solidifies  when  strongly  cooled.  The  melting  point 
lies  between  11  and  12°.  Oxidized  with  a  boiling  :i  p.  c.  permanga- 
nate solution  it  yields  terephtalic  acid,  C6H4(COOH)2.  When 
treated  with  fuming  sulphuric  acid  p-octyl  toluene  sulphonic  acid, 
C8Hi7.CoH3(S03H).CH3,  results,  of  which  the  barium  (  +  H2O),  lead 
(+4H20)  and  copper  (-f2%H20)  salts  were  prepared.  With  fuming 
nitric  acid  it  yields  mononitro  p-octyl  toluene,  CsHii.CoHstNC^.CHs 
and  dinitro-p-octyl  toluene,  CsHiT.Cot^NC^b.nis.  Treatment  with 
acetyl  chloride  results  in  the  formation  of  octyl-tolyl-methyl  ketone, 
C8Hi7.CoH4(CH8)CO.CH3. 

56.    Trivalerylene. 

In  1867  Reboul2  obtained,  by  treating  valerylene  with  cone 
sulphuric  acid,  an  oil  from  which,  after  washing  and  drying,  there 
could  be  separated  by  distillation  a  fraction  boiling  at  175—177° 
corresponding  to  the  formula  CioHi»j.H20,  and  a  hydrocarbon 
Cir>H24  boiling  between  265 — 275°,  and  having  a  specific  gravity  of 
0.862  at  15°.  Diluted  sulphuric  acid  has  a  similar  action  on  valery- 
lene. 

By  heating  valerylene  in  sealed  tubes  to  250—260°  Bouchardat3 
in  1878  obtained  a  hydrocarbon  CioHi6  and  an  other  Cir>H24.  The 
latter  compound  boiled  between  240 — 250°  and  gave  a  monochlor- 
hydrate  which  was  decomposed  by  heat. 

57.   Yetivene. 

Gladstone4  in  1872  obtained  from  oil  of  vetiver,  by  destroying 


1  Ber.,  81,  p.  940. 

2  Compt.  rend.,  64,  p.  410;   Ann.,  143,  p.  373. 

s   Compt.  rend.,  87,  p.  654;    Bull.  Soc.  chim.,  83,  p.  24. 
*  Journ.  Pharm.,  31.  pp.  (J87,  705. 


121 

the  oxygenated  constituents  by  means  of  sodium,  a  small  amount 
of  n  rather  viscid  hydrocarbon,  of  the  following  properties: 
B.  p.  255°;  (1  =  0.9332;  NA=  1.5061. 

Gladstone  did  not  have  this  compound,  which  he  considers  to  be 
a  sesquiterpene,  in  a  pure  condition. 

Genvresse  and  Langlois l  separated  from  oil  of  vetiver  a  ses- 
quiterpene by  fractional  distillation  and  three  rectifications  from 
sodium.  To  this  fraction  the}'  gave  the  name  of  vetivene.  It  is  a 
colorless,  mobile  liquid  of  the  following  properties:  d2o°  =  0.982; 
«nl5°=  +18°  19';  b.  p.  135°  (15  mm.),  262—263°  (740  mm.). 

It  absorbs  four  atoms  of  bromine,  without  disengaging  hydro- 
bromic  acid;  the  liquid  is  colored  blue. 

Vetivenol,  CisHtaeO,  also  found  by  Genvresse  and  Langlois, 
has  the  following  properties:  d2o°— 1.011;  o.^—  +53°  43' in  alcoholic 
solution;  b.  p.  169—170°  (15  mm.). 

According  to  these  chemists  dehydrating  agents  give  rise  to  a 
sesquiterpene  of  the  general  properties  of  vetivene. 

58.    Winterene. 

By  the  action  of  sodium  on  the  oil  obtained  by  steam  distillation 
from  Winter's  bark  and  subsequent  fractionation,  Arata  and  Can- 
zonari2  obtained  the  following  fractions;  1.  —250°;  2.  250—260°; 
3.  260—270°;  4.  270—280°.  Fraction  260— 270°  had  the  sp.  gr. 
0.9344  at  13°.  The  original  oil  was  dextrogyrate  and  fraction 
255—270°  showed  a  rotation  of  +11.2°.  Fraction  260—265°  made 
up  the  bulk  of  the  oil  and  was  called  by  them  winterene.  The  index 
of  refraction  of  this  fraction  was  1.4931.  It  had  the  composition 
CsHs,  and  in  accordance  with  the  vapor  density  11.67  the  authors 
gave  to  winterene  the  formula  C2sH4o.  This  is  doubtful,  as  the  com- 
pound readily  absorbs  oxygen  from  the  air.  Moreover,  the  boiling 
point  is  rather  low  for  so  complex  a  substance,  corresponding  rather 
with  that  of  the  sesquiterpenes.  With  hydrochloric  acid  it  yields  a 
liquid  addition  product  having  a  camphoraceous  odor.  The  chemical 
work  done  on  this  substance  is  meagre,  being  restricted  almost 
entirely  to  color  reactions.  The  subject  seems  well  worthy  of  further 


1  Compt.  rend.,  13;",  p.  1059. 

2  Armies  tie  la  Cientiflea  Argentina;   Drugg.  Bull.,  1880,  p.  140:   Arch.  d.  Pharm., 
227,  p.  818;  Jahresb.  f.  Pharm. ,  1889,  p.  70;   Pharm.  Ztgn  1889,  p.  888. 


122 

investigation  in  the  light  of  the  more  recent  work  on  the  sesquiter- 
penes. 

59.    Zingiberene. 
General  Discussion  and  History. 

Zingiberene  has  so  far  been  found  only  in  ginger  oil.  The  first 
investigation  of  ginger  oil  was  made  by  Papousek1  in  1853,  who  did 
not,  however,  recognize  the  sesquiterpene.  Thresh2  in  1881  found 
the  major  portion  of  the  oil  to  consist  of  a  sesquiterpene  boiling 
between  256—260°.  This  fraction  had  a  specific  gravity  of  0.899 
and  a  rotatory  power  of  —16.10°.  Nitroso  derivatives  of  the  ses- 
quiterpenes  were  unknown  at  that  time,  so  that  Thresh  was  limited 
in  his  investigation  to  the  attempt  to  prepare  a  hydrochloride, 
which  failed. 

In  1900  v.  Soden  and  Rojahn3  published  the  results  of  an  ex- 
amination of  the  sesquiterpene  of  ginger  oil.  It  had  a  specific  gravity 
of  0.872  at  15°  and  a  rotation  of  —69°.  By  titration  with  bromine 
in  glacial  acetic  acid  solution,  they  determined  the  presence  of  two 
ethylene  bonds.  The  tetrabromide  formed  could  not  be  obtained  in 
a  crystalline  condition.  The  hydrochloric  acid  and  hydrobromic  acid 
addition  products  are  reported  as  brown,  viscous  oils.  Attempts  to 
prepare  a  nitrosochloride  and  a  nitrosate  failed. 

The  physical  properties,  specific  gravity  and  rotatory  power  of 
this  sesquiterpene  did  not  agree  with  any  of  the  known  sesquiter- 
penes,  and  v.  Soden  and  Rojahn,  therefore,  proposed  the  name  of 
zingiberene  for  the  sesquiterpene. 

Schreiner  and  Kremers4  published  their  results  obtained  with 
zingiberene  somewhat  later.  While  the  physical  constants  found  by 
them  agree  in  the  main  with  those  of  v.  Soden  and  Rojahn,  their 
chemical  results  are  different  as  they  succeeded  in  preparing  a 
dihydrochloride,  a  nitrosochloride,  a  nitrosate  and  a  nitrosite,  thus 
definitely  characterizing  this  sesquiterpene. 

The  low  specific  gravity  of  zingiberene  is  striking,  and  it,  to- 
gether with  its  molecular  refraction  indicate  the  presence  of  more 
double  bonds  and  less  cycles  than  are  present  in  most  other  ses- 
quiterpenes.  The  molecular  refraction  of  zingiberene  speaks  strongly 
for  three  double  bonds  but  its  chemical  derivatives  so  far  prepared 


1  Journ.  Pharm.  Chirn.,  (3),  23,  p.  46J 

2  Pharm.  Journ.,  (3),  12,  p.  243. 

8   Pharm.  Archives,  4,  pp.  61,  155. 


123 

are  not  concordant.  Thus,  for  instance,  it  forms  a  well  crystallized 
dihydrochloride.  This  disagreement  is  similar  to  that  which  existed 
in  the  case  of  caryophyllene,  but  later  chemical  work  confirmed 
the  optical  method.  The  optical  method  is  probably  the  must  trust- 
worthy in  this  case,  for  the  following  reasons: 

1.  The    optical  method  has  proven  trustworthy  in  the  case  of 
caryophyllene  and  with  a  large  number  of  compounds  in  other  fields 
of   research.    The   argument  that  the  zingiberene  subjected   to   the 
optical  test  was  not  absolutely  pure,  being  obtained  by  fractional 
distillation,  while  true,  has  but  little  bearing  on  this  question.    The 
properties  of   the   ginger    fractions,    show  that    those   immediately 
preceding    and     following   the    zingiberene    fraction    are    higher    in 
specific   gravity  than    the   zingiberene.    Any   admixture  with    these 
would,  therefore,  increase  the  specific  gravity  of  the  zingiberene.    It 
is,  however,  the  very  low  specific  gravity  of  this  compound  which 
causes  the  result  to  come  out  for  three  double  bonds.    The  specific 
gravity  is  a  far  more  sensitive  factor  in  the  formula  ^^-^  than 
is  the  index  of  refraction. 

2.  The  sesquiterpene  has  a  much  lower  specific  gravity  than  the 
sesquiterpenes  with    only  two    double   bonds.    This   is,    however,    a 
change  concomitant  with  the  introduction  of  double  bonds,  the  com- 
position remaining  unchanged. 

3.  It  is  almost  always  far  more  difficult  to  form  a  tri-derivative 
than  a  mono-  or  di-derivative.  The  dihydrochloride  would  of  course, 
form   first,    and    being  a  crystalline  compound,    may  separate  out. 
The   tri-hydrochloride  would    form  with  much   greater   difficulty,    if 
indeed  it  can  be  formed  at  all.    Moreover,    an    inversion    with   the 
production  of  an  isomeric  sesquiterpene,  as  occurs  evidently  in  the 
preparation    of  caryophyllene  hydrate,  and  which  is  also  discussed 
under   cadinene   and   its   dihydrochloride,    is   not   excluded.    In   the 
bromine  titration,  hydrobromic  acid  is  given  off,  so  this  method  of 
testing  for  the  number  of  double  bonds  becomes  untrustworthy. 

Further  work  is  necessary  before  this  question  can  be  definitely 

decided. 

Preparation. 

Zingiberene  is  obtained  by  the  fractional  distillation  of  ginger 
oil.  v.  Soden  and  Ilojahn  fractionated  the  oil  under  a  pressure  of 
8—10  mm.  The  portion  going  over  at  120—125°  was  saponified 


124 

with  alcoholic  potash  and  the  washed  oil  again  fractionated  in  a 
vacuum.  Schreiner  and  Kremers3  proceeded  in  a  similar  manner, 
collecting  fraction  150 — 160°  (32  mm.),  saponifying  this  and  again 
fractionating,  collecting  fraction  160— 1G2°. 

Physical  Properties. 

.     The  physical  constants  of  zingiberene  are  as  follows: 
"Thresh  (1881):  B.  p.  256-260°;  d  =  0.899 ;  «„  =  -16.10°. 
v.  Soden  and  Rojahn   (1900):   B.  p.   134°   (14  mm.);   269—270° 

(760mm.);  di5°=0.872;  au=  -69°. 
Schreiner    and    Kremers    (1901):     B.    p.    160—161°    (32    mm.); 

dao°  =  0.8731;   [«]»=  -73.38°;  nD  =  1.49399. 
The  molecular  refraction  was  67.87;  the  calculated  molecular  re- 
fraction, assuming  three  double  bonds,  is  67.86. 

Schreiner  and  Kremers  also  determined  the  indices  of  refraction 
from  the  three  hydrogen  lines.  They  were  as  follows: 

Ha  =  1.49041.        H0  =  1.50319.        Hr  =  1.51112. 

Zingiberene  is  a  colorless,  mobile  liquid,  but  readily  msinifies  and 
becomes  viscous.  It  is  readily  soluble  in  ether,  petroleum  ether, 
benzene  and  absolute  alcohol,  more  sparingly  (1:16)  in  ordinary 
alcohol. 

Chemical  Properties. 

Zingiberene  readily  absorbs  oxygen  from  the  air.  Bromine  com- 
bines with  it,  but  as  hydrobromic  acid  is  formed,  no  bromide  could 
be  obtained.  With  hydrochloric  acid  it  combines  to  form  a  dihydro- 
chloride,  and  with  nitrosylchloride  and  the  oxides  of  nitrogen  to 
for  a  nitrosochloride,  a  nitrosite  and  a  nitrosate  respectively. 

Zingiberene  dihydrochloride,  CisHa^SHCl.  Thresh4  in 
1881  attempted  to  prepare  the  hydrochloride  by  passing  the  dry  gas 
into  an  ethereal  solution  of  the  sesquiterpene  fraction,  but  no  crystal- 
line compound  could  be  obtained.  Thresh  attempted  to  remove  the 
excess  of  hydrochloric  acid  by  heating  in  a  current  of  dry  hydrogen 
until  the  escaping  gas  no  longer  reddened  moistened  blue  litmus 
paper.  The  result  was  unsatisfactory,  as  analysis  showed  only  5.47 
p.  c.  of  HC1,  corresponding  to  the  improbable  formula 
The  specific  gravity  of  this  liquid  was  0.9246. 

a  Pharni.  Archives,  4,  p.  155. 
±   Pharm.  Journ.,  (3),  12,  p.  245, 


125 

Von  Soden  and  Rojahn  report  the  hydrochloric  acid  addition 
product  as  a  brown  viscous  oil  but  Schreiner  and  Kremers5  obtained 
this  derivative  in  a  crystalline  form.  It  is  prepared  as  follows: 

Zingiberene  is  dissolved  in  an  equal  volume  of  glacial  acetic  acid 
and  the  solution  saturated  with  dry  hydrochloric  acid  gas  at  0°. 
The  solution  is  then  allowed  to  stand  for  a  day  or  two,  after 
which  time  the  dark  colored  liquid  will  be  found  to  be  interspersed 
with  fine  needles.  These  are  collected  on  a  force  filter  and  washed 
with  cold  alcohol.  A  second  crop  can  usually  be  obtained  by  again 
saturating  the  mother  liquor  with  dry  hydrochloric  acid  gas.  When 
recrystaHized  from  hot  alcohol,  the  dihydrochloride  is  pure  white 
and  melts  at  108—169°. 

Zingiberene  nitrosochloride.  Schreiner  and  Kremers  pre- 
pared this  as  follows: 

A  small  portion  of  zingiberene  is  dissolved  in  an  equal  volume  of 
glacial  acetic  acid  and  of  ethyl  nitrite.  After  cooling  in  a  freezing 
mixture,  it  is  gradually  treated  with  twice  the  volume  of  zingiberene 
used,  of  a  saturated  solution  of  hydrochloric  acid  gas  in  glacial  acetic 
acid.  After  a  minute  or  two  the  reacting  mixture  is  treated  with 
twice  its  volume  of  alcohol,  continually  agitating.  The  nitroso- 
chloride separates  out  as  a  flo^culent  precipitate.  This  is  collected 
on  a  force  filter  and  well  washed  with  cold  alcohol.  It  is  a  fine  white 
powder,  and  may  be  purified  by  dissolving  in  ethyl  acetate  and 
precipitating  with  alcohol.  Thus  obtained,  it  melts  at  96 — 97°  with 
decomposition. 

Zingiberene  nitrosate.  This  derivative  does  not  separate 
when  the  hydrocarbon  is  treated  in  the  usual  manner,  but  with  a 
slight  modification  it  separates  in  large  quantities,  the  yield  being 
almost  theoretical.  The  procedure  is  as  follows: 

A  small  portion  of  zingiberene  is  dissolved  in  an  equal  volume 
of  glacial  acetic  acid  and  of  ethyl  nitrite.  This  mixture  is  well  cooled 
in  a  freezing  mixture  and  then  treated  slowly  with  a  mixture  of 
nitric  acid  and  glacial  acetic  acid,  each  equal  in  volume  to  the 
zingiberene  used.  The  first  few  drops  produce  a  deep  bluish-green  color 
which  rapidly  fades.  The  mixture  remains  clear  but  becomes  quite 
thick,  and  toward  the  end  of  the  reaction  turbid  and  exceedingly 
viscous.  At  this  stage  the  mixture  is  treated  with  about  four  times 
its  volume  of  cold  alcohol,  and  on  shaking,  large  quantities  of  the 

s   Pharm.  Archives,  4,  p.  161. 


126 

nitrosate  separate.  This  is  collected  on  a  force  filter,  washed  \vith 
alcohol  and  dried  on  a  porous  plate.  Attempts  to  purify  the  product 
by  crystallization  have  so  far  been  unsuccessful.  The  compound  may 
be  purified  by  dissolving  in  ethyl  acetate  and  precipitating  with 
alcohol.  It  is  a  slightly  yellowish  powder  melting  at  86 — 88°  with 
decomposition. 

ftingiberene  nitrosite.  This  derivative  is  more  readily  ob- 
tained than  the  other  nitroso-compounds  of  this  sesquiterpene.  It 
can  be  obtained  in  a  pure  state  with  comparative  ease  if  the 
recrystallization  is  done  on  a  small  quantity  and  with  but  a 
momentary  application  of  heat.  When  so  purified  its  melting  point 
is  sharp  and  the  compound  is,  therefore,  well  suited  for  identifying 
the  sesquiterpene.  Schreiner  and  Krerners  prepared  this  derivative 
as  follows: 

A  small  portion  of  zingiberene  is  dissolved  in  about  10  times  its 
volume  of  petroleum  ether  and  is  then  cooled  in  ice  water  or  a  freez- 
ing mixture.  It  is  then  treated  with  a  volume  equal  to  the  zingi- 
berene used,  of  a  saturated  solution  of  sodium  nitrite,  and  the  same 
amount  of  glacial  acetic  a,cid.  The  liquid  shows  a  passing  blue 
color  and  on  shaking  solidifies  completely  to  a  mass  of  white  crystals. 
The  magma  is  best  transferred  to  a  cloth  and  washed  with  cold 
water  and  pressed.  After  spreading  on  a  porous  plate  for  a 
short  time  the  compound  must  be  purified  at  once,  as  it  readily  de- 
composes when  in  an  impure  condition.  This  is  best  done  by  re- 
crystallizing  from  hot  methyl  alcohol,  working  with  small  portions 
at  a  time  and  avoiding  heating  for  any  length  of  time.  If  heated 
for  only  a  few  moments  crystals  will  be  obtained.  Even  a  momentary 
heating  will  result  in  considerable  loss,  but  the  crystals  which 
separate  are  fine  silky  needles,  and  after  washing  are  quite  pure. 
If  thought  necessary  the  operation  may  be  repeated.  Thus  purified 
the  compound  melts  at  97—98°.  It  is  much  less  stable  than  the 
corresponding  caryophyllene  compound.  After  keeping  for  a  few 
weeks  it  becomes  yellow  and  soon  changes  to  a  black,  sticky  mass. 


127 


I IV 


Abies  alba 28,  4() 

Acorns  calamus, 27,  28 

—  spuriosus 27,  28,  58,  107 

Ageratuin  conyzoides, 81,  106 

Alliutn  sativum 28 

Amyrene ., 34 

Amvris  balsamifera, 30,  3;",  47,  106 

Amyrol 58,  30.  106 

—  Sesquiterpene  from 106 

Andropojfon  muriaticuH 28 

—  nardus,.. 28 

Anonaceae,  .*. 29,  44 

Apium  graveolens 31 

Araceae ' 28 

Aralia  nudicaulis 27,  3() 

Aralinceae, 3O 

Araliene 17,  21,  27,  30 

Archangel ica  offlcinalis, 31 

ArtemesiH  absinthium 31,  49 

Atractylene 32 

Arractylis  ovata 31,  32 

Atractylol 31.  32 

Benzene,  inethvl — isopropvl— isoani vl, 

'. "! 24,  119 

octvl— methyl 24,   120 

BisaboleiiP '. 17,   21,  30,  33 

-  Trlhydrochlorlde 38 

Boiling  points  of  se8quiterpenes,...20,  21 

Hoswellia  carterii 30,  47 

Bulnesia  sarmienti 29 

Bursera  aloexylon 30 

B u  rse i-acea  e 30,  47 

Cadinene 17,  20,  34 

—  ( 'liemical   properties 52 

Derivatives 52 

Dextrogyrate 41,  42,  47,  55 

Dihydrio.lide 55 

—  Dihydrobromide 55 

—  Dihydrochloride, 53 

—  Discussion, 35 

-  History 35 

Nitrosat" 56 

—  Xitrosochloride 56 

—  Occurrence 28,  39 


Oxygenated  compounds  yielding, ..57 

Physical  properties, 51 

—  Preparation, 50 

—  Synonyms, 34 

Calaniene 21,  28,  58 

Calamol, 28 

('uinphene 7 

of  clove  oil, 60 

orders  of, 5,  6 

Campherenes 6 

Caniphilenes 6,  7 

Camphol  series 7 

Cananga  odorata, 29,  44 

Canella  alba, 30,  66 

ranellaeeae, 30,  66- 

ran  n  abene 113 

Cannabis  gigantea 29,  113 

sativa, 29 

Caparrapene 17,  21,  29,  58 

Chemical  properties 59 

Dihydrochloride 59 

—  Physical  properties 59 

—  Preparation ..59 

raparrapiol, 29,  59 

( 'arlina  acaulis,  31 

Caryophyllene 17,  20,  60 

Acetate 78 

Bromide 77 

Chemical  properties 69 

Chloride 77 

Derivatives, 69  • 

Dihydrochloride 7O- 

—  Sesquiterpene  from 1O8: 

Discussion, *>1 

History 61 

Hydrate 76 

Iodide 78 

Nitrate 78 

NitroT  benzylamine,  <t- 75^ 

piperidine 76 

Xitrosate 72 

Nitrosite 73 

—  ^-compound 74 

^-compound 75 


128 


Nitrosochloride 71 

Occurrence, 28,  «3 

Physical  properties 68 

Preparation 67 

Synonyms, 60 

-  (•'rcthane,. 79 

Cedrela  odorata 3<>,  48 

Cedrene,    as  synonvm   for    sesquiter- 

pene, ...  K).  34.  60.  118 

Cedrenes, 17,  20,  28,  79 

Chemical  properties, 81 

—  Discussion, 79 

History 79 

Physical  properties, 81 

Preparation 80 

Cedrol 28,  82 

Cedrone, 81 

Cedrus  atlantica 41,  51,  55 

libani 41 

Characterized  sesquiterpenes,  compari- 
son of, 20 

Cinnamomum  e amphora, 29,  45 

Citrus  bigaradia 4,  3O,  47 

limonum 30 

lu  mia 4 

Citrenes lo 

Classification  of  sesquiterpenes, 13,  17 

—  early, 11 

of  terpenes,  history, 4 

Clovene 17,  21,  83 

Colophene, 8 

Commiphora  species 30 

Comparison  of  sesquiterpenes, 17 

—  Tables 20,  21 

Compositae, 31,  49 

Conimene 30,  83 

Constitution  of  sesquiterpenes, 17 

of  terpenes, 9 

Convulvulaceae, 31 

Convulvulus  floridus, 31 

-^ —  scoparius 31 

Copaifera  officinalis, 29,  64 

Copaivene, 60 

Croton  eluteria 30 

Cubebene, 34,  83 

Cubebenol,  aetherisches, 34 

Cubeb  camphor, 28,  84 

Cupressus  sempervirens, 112 

Cusparia  trifoliata, SO,  35.  46 

Cypress  camphor 112 

Di p terocarpaceae 30,  48 

Dipterocarpus  species 30 

turbinatus, 30 

Diterpene, 1,  11 

--as  synonym 6O 

Drimys  winteri, 29 

Dryobalanops  camphora,..3O,  35,  48,  .">:$ 

Krechthites  hieracifolia, 31 

Ericaceae 31 

Eugenia  caryophyllata 30,  66 

Euphorbiaceae 3O 

Ferula  asa  foetida 31,  48 

rubricaulis, 31,  49 

Galipea  cusparia 35 

Galipene, 17,  21,  30,  34,  84 

Galipol 30.  57 

Gonorol, 104 

Gramineae, 28 

Group,  fifteen  carbon, 8 

ten  carbon, 8 

of  sesquiterpenes.  chain,. ..I'',  17,  22 

dicyclic 13,  17,  19 

chart, 15 


monocyclic,   13.  17,  22 

chart, 14 

tetracyclic 13,  17,  18 

tricyclic 13,  17,  18 

of  terpenes, 5 

orange, 9 

—  turpentine, 9 

Guajene, 17,  21.  S5 

Guajol 29.  85 

Gurjunene 21,  80,  86 

Hemiterpenes, 1,  11 

He veene, s  7 

Humulene, 17,  2(),  87 

Chemical  properties, 91 

Derivatives, 91 

Dihydrochloride, 92 

Discussion, 88 

History, ss 

Iso-nitrosite 93 

Fso-nitroso- 95 

Nitrol  benzylamine, 94 

hydrochloride 94 

piperidine, «>4 

— hydrochloride, 94 

platino  chloride, 95 

Nitrosate, 93 

Nitrosite 93 

—  Nitroso-, 95 

Nitrosochloride, 92 

Occurrence 28,  89 

—  Physical  properties, 91 

Preparati  on 90 

Synonyms 87 

Humulus  lupulus 29,  87,  9(> 

Hydrates  of  sesquiterpenes.  occurrence 

of, 28 

Icira  heptaphylla, 3O 

Iso-cedrol, 82 

nitroso  humulene 95 

santalenes, 104 

terpenes 10 

Isomerism,  chemical, 5 

genetic, 4 

Isoprene,  1,  24 

Juniperus   communis, 28,  41 

oxvredrus 28.  41 

saitina i>8.  42 

—  virginiana, 26,  27,  28.  42 


Kampferia  galanga,. 


28,  114 


Labiatae, 31 ,  49 

L  a  u 1  •  a  c  e  a  e —  29,  45 

Laurus  npbilis 29 

Lava nd uia  spica :-51 

vera, 31 

I.edene 21,  95 

—  hydrate 31,  96 

Ledum  camphor 31,  96 

Ledum  palustre 31 ,  96 

Legu  m in  osae 29.  64 

Liliaceae 2S 

Magiiolinceae 29 

Meliaceae 30.  48 

Melting  points   of    sesquit>-rpene    deri- 
vatives,  20,  21 

Mentha  arvensis  var.  pipernfecehs 31 

—  piperitn 31,  49 

Meta  cani])henes (> 

pyrolenes 7 

M oni m ia ceae 29,  45 

Moi-Hceae, 29,  9O 

Alvrtaci'iie, 30,  66 


129 


Neetandra  caparrapi 29 

Nitrolamines 2 

Nitrosates 2 

Nitrosites, 2 

Nitroso-humulene 95 

—  nitro-compounds  2 

Nitrosochlorides 2 

Nuclear  types  of  sesquiterpenes 16 

Occurrence  of  sesquiterpenes 26 

Table 2S 

Ocimum  basilicum HI,  1O7 

Oil  of  Ageratum 106 

—  Angelica  root 107 

—  Angostura  bark 46,  57,  84 

Asafetida 48,  57 

Atlas  cedar 41 

-  Basilicum 107 

Betel  leaves 44 

—  Bisabol  myrrh 33 

Cade 41 

Calamus, 58 

Japanese 58,  107 

—  Camphor, 45 

—  Can  anga, 44 

Canella, 66 

Caparrapi 58 

Carline  thistle, 21,  107 

—  Cascarilla 21,  109 

Cedar  leaves 42 

wood 79 

Cedrela  wood, 48 

—  Celery  seed 109 

Citronella 17,  21,  110 

Cloves, 66 

,  indifferent 60 

Clove  stems 67 

Comma  resin, 83 

Copaiba, 64 

—  balsam,  African Ill 

Cubebs 43,  112 

Cypress 112 

Dryobalanops  camphora 48 

Erechthites 112 

Frankincense 47 

Galbanum 49 

Garlic 112 

Ginger 122 

Golden  rod 49 

Guaiac    wood 85 

—  Gurjun  balsam, 86 

Hemlock  needle, 40,  113 

-  Hemp, 21,  11« 

—  Mops 90 

—  Juniper  berries 41 

—  Kampferia  gal  anga, 114 

Kesso  root 114 

Laurel  berries, 21.  114 

Lavender 115 

—  Ledum  palustre 95 

—  Lemon 

—  Linaloe 

—  Minjak  Lagam  balsam 

—  Ollbanum 

—  Paracopaiba, 


115 

115 

21.  116 

47 

....60 


Pa rac  >  to  bark 45 

Patchouly 49,  97 

—  Pepper,  black :42,  64 

—  long 115 

—  Peppermint,  American 49 

—  Knglish, 117 

Japanese, 117 

—  Petitgrain 47 

—  Pimenta 21,  117 

—  I'ine  needle, 4(> 

Poplar  buds 89.  118 

—  Rhodium 98 

Rosewood...  ....98 


Sage.  Knglish, 1  IS 

Sandal  wood,  East  Indian, 98 

West  Indian, 47,  58,   lm; 

Sassafras, 4  ~, 

—  leaf 4") 

Savin 4ii 

Spike 119 

Spiraea 119 

Valerian, .21,  119 

Vetiver 120 

Wild  thyme, 1  1 «.» 

Winter's  bark 121 

Wormwood, 49 

Ylang  Ylang 44 

Paracamphenes, 6,  34,  6O 

Paraterebenthenes, 7 

Patchonlene 17,  21,  97 

Patchoulj-  alcohol, 31,  '.17 

Pentenes, 11 

Picea  excelsa, 28,  40 

Pimenta  officinalis, 3O 

Pinaceae 28,  4O 

Pinus  m  on  tan  a 28,  4O 

silvestris 28,  4O 

Piper  betle 26,  28,  44 

cubeba 26,  28,  43 

nigrum, 26.  28,  42,  (>4 

Piperaceae, ..28,  42,  64 

Pogostemon  patchouly, 31,  49 

Polyterpenes, 1,  11 

Populus  nigra 29,  S9 

Pyrolenes 7 

Refraction     of    sesquiterpenes,    index 

of 20.  21 

molecular 17 

Rhodiene, 17,  31,  98 

Rosaceae, 29 

Rotation  of  sesquiterpenes,  optical,  2O,  21 
Rutaceae, 30,  46,  106 

A 

Salicaceae 29,  89 

Salvia  officinalis, 31 

Santalaceae, 29 

Santalenes 17,  2O,  98 

Acetate 104 

Chemical  properties 102 

Derivatives, 102 

Dihydrochloride, 102 

Discussion, 98 

History 98 

—  Hydrate 104 

Iso- 104 

Nitrol  piperidines, 103 

Nitrosochlorides 103 

—  Occurrence, 28,  98 

Physical  properties, 101 

—  Preparation, 101 

—  Separation  of  a-  and  ,5-, 101 

Santalal 100,  101 

Santalol, 29,  100,  104 

—  Separation   into  a-  and  jj-, 105 

Sa  n  t al  u  in  album 29 

Santonin,  sesquiterpene  from, 118 

Sassafras  offlcinale 29,  45 

Sesquiterebene 34.  60 

Sesquiterebenthene, 34,  60 

Sesquiterpene,  as  synonym, 34,  60 

Sesquiterpenes,    position   in    systems 
of  terpenes  at  large 4 

position     in     modern     rational 

svstem  of  hydrocarbons, 13 

Solidago  canadensis, 31 

Specific    gravities    of    sesquiterpenes, 

...17,  20,  21 


Spiraea  ulinaria 2'.» 

Synthesis  of  sesquiterpenes 17.  23 

Synthetic  sesquiterpenes 23.  11'.) 


Terebenes 7 

Tereben  t  henes, 0 

—  Monatomic 7 

—  Diatomic, 7 

Terpenes 1 .   11 

—  Classification, 4 

—  Constitution, 9 

—  Introduction  of  term i.  8 

—  Orange  group 9 

—  Saturation  capacity  of 1O 

-  Turpentine  group, .". 9 

Terpil  series, 7 

Terpilenee 7 

Te  t  rapen  tenes 11 

Thvnms  serphylluui,. 31 

Tri'pentenes, ...'. 11 

Trivalerylene, ..12O 

Tsnga  cimadensis 2s,  40 


[Jm  belli  ferae,...  ....31.  -ts 


Dncharacterized  sewitriterpenes,  com- 
parison of  .......................................  21 

--  Occurrence  of,  .........................  2M 

Vak'riana  of  lie-in  a  lis  ..............................  31 

—  var.  aiiffustifolia,  ....................  31 

Valerianaceae,....  ...................................  31 


Vetivcnol,  ............................................  121 

Wiuterene,  ..............................  21,  2'.),  121 

Zingiber  officinale  .................................  2S 

Zingiberai-eao,  .......................................  28 

-em'  .............................  17,  20,  122 

Chemical  properties  .....................  124- 

-  Dihydrochlorule  ...........................  1  24 

—  Discussion  ....................................  122 

--  History  ........................................  122 

-  N'itrosate,  .....................................  125 

-  Nitrosite  .......................................  12f, 

-  Nitrosochloride  ....................  ........  1  25 

--  Occurrence  .............................  28,   122 

--  Physical  properties,...  .................  124 

-  Preparation  ................................  123 

Zyj?ophyllaceae,  ...................................  29 


A2.0 


